Considerable controversy exists regarding the relation between maternal caffeine intake during pregnancy and risk of low birth weight . We aim to assess this association using a systematic review and dose–response meta-analysis of prospective studies.Potential articles were identified by searching MEDLINE and SCOPUS databases through 17 July 2013. Two authors independently extracted information on study design, participant characteristics and estimates of associations. Random-effects models were used to derive the summary relative risks (RRs) and corresponding 95% confidence intervals (CIs). Dose–response relationships were assessed using generalized least-squares trend estimation.I2 0.0%) for low intake (50 to 149 mg/day), 1.38  for moderate intake (150 to 349 mg/day), and 1.60  for high intake (≥350 mg/day). In the dose–response analysis, each 100-mg/day increment in maternal caffeine intake (around one cup of coffee) was associated with 13%  higher risk of low birth weight. The association persisted in strata defined according to various study characteristics. Moderate  and high  caffeine intakes were also associated with a significantly lower birth weight as compared with the reference category.In our meta-analysis, we included 13 prospective studies: 9 with low birth weight as a binary outcome variable  and 6 with birth weight as a continuous outcome variable . Compared with the reference category with no or very low caffeine intake, the RR (95% CI) of low birth weight was 1.13  contains supplementary material, which is available to authorized users. Globally, it has been estimated that 15.5% of all infants are born low birth weight, defined as birth weight less than 2,500 g .Caffeine is a plant alkaloid found mainly in coffee, tea, cola soft drinks and cocoa . It is tAs many women consume caffeine-containing food and beverages during pregnancy, the possible harmful effects of caffeine intake on fetal and birth outcomes warrant evaluation ,14,15. AThis meta-analysis was conducted and reported in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline [see Additional file Two investigators (L-WC and YW) searched MEDLINE and SCOPUS databases through 17 July 2013 with no language restriction. SCOPUS is an abstract and citation database of peer-reviewed literature that includes all the contents from the EMBASE database . The seaStudies were included if they met the following criteria: (1) the study reported data from an original, peer-reviewed study ; (2) the study was a prospective cohort study or nested case–control study; and (3) the authors reported the risk estimates of low birth weight associated with maternal caffeine intake  during pregnancy. We excluded studies that only presented crude estimates or did not consider potential confounding by smoking and studies conducted in unhealthy populations . We also excluded animal studies, case reports or case series, cross-sectional studies, retrospective case–control studies and other studies that assessed caffeine intake after the occurrence of outcome.th percentile for gestational age. IUGR is officially defined as estimated fetal weight less than the 10th percentile for gestational age [Low birth weight was defined as birth weight less than 2,500 g and SGA was defined as birth weight less than the 10onal age ,20, but The study selection was independently conducted by two authors (L-WC and YW). We also considered non-English articles with help from colleagues who are proficient in these languages. The inter-rater agreement was fairly good . Discreet al. defined SGA using three methods and we abstracted the effect estimates for outcome defined using Skjaerven’s method as similar methods were used in other studies included in our meta-analysis [For included studies, information on study, participants, measurement of exposure and outcome, effect estimates and their standard errors (or related statistics) were extracted independently by two investigators (L-WC and YW) using a standardized extraction form. Discrepancies were resolved by discussion with a third investigator (RMvD). Study quality assessment was done by considering characteristics such as study design, number of cases and participants, method of exposure assessment and adjustment of confounders. Sengpiel analysis .Multivariable-adjusted odds ratios (ORs), hazard ratios (HRs) or relative risks (RRs) have been used in different studies, and we chose RRs as measures of risk estimates in the meta-analysis because the incident rate was low and OR and HR thus approximated RR . For stuDifferent studies used different cutoff points for the caffeine intake categories. To combine the risk estimates from different categories in different studies, we assigned the median value for each category of caffeine intake. When lower and upper boundaries were presented for the category, we assigned the midpoint as an estimate of the median caffeine intake. If the upper boundary of the highest category was not provided, we assumed that the boundary had the same amplitude as the second-highest category . If the We first conducted analyses based on different levels of caffeine consumption. We identified four levels of caffeine consumption based on assigned median caffeine consumption level: (1) reference category, (2) low caffeine consumption 50 to 149 mg/day), (3) moderate caffeine consumption 150 to 349 mg/day) and (4) high caffeine consumption ≥350 mg/day). The median caffeine levels for the reference category were 0 mg/day in five studies ,30-33 an mg/day, 9 mg/day 0 mg/day.I2 statistic were used to evaluate statistical heterogeneity among studies [I2 values of 25%, 50% and 75% correspond to low, moderate and high degrees of heterogeneity, respectively [Effect estimates of the individual studies were combined using the random-effects method as described by DerSimonian and Laird , which c studies ,38, and P-value for non-linearity was obtained by testing the null hypothesis that the spline term is equal to 0.We further conducted a dose–response analysis (for binary outcomes) using the generalized least-squares trend estimation (GLST) method as described by Greenland and Longnecker ,40, whicP-values <0.05 were considered statistically significant.We conducted stratified analyses and meta-regression analyses to assess potential sources of heterogeneity by different study-level characteristics. We conducted sensitivity analysis to assess the influence of each individual study by omitting one study at a time and calculating the summary RR for the remaining studies. Publication bias was evaluated with the Egger’s regression test, Begg’s adjusted rank correlation test and visual inspection of funnel plot ,42. All The flow diagram with details of the study selection is shown in Figure I2 = 0.0% for low caffeine intake, 31.9% for moderate caffeine intake and 65.8% for high caffeine intake.Figure P = 0.89), we assumed a linear relationship. The summary RR was 1.13  than for the categorical comparisons. However, the summary RRs did not substantially differ by various study characteristics including age of the mothers, region, year of publication, size of the study population, exposure assessment , questionnaire administration for exposure assessment (self-administered or interviewer-administered), assessed period of exposure during pregnancy, outcome definition  and adjustment for smoking (a few or multiple categories) . As the results in the study by Brooke et al. were reported separately for smokers and non-smokers, the potential impact of including two data points from the same study was assessed by excluding either of the data points, but the heterogeneity remained low . For studies that were included for qualitative review only [see Additional file We also conducted a meta-analysis of studies of caffeine intake and birth weight as a continuous outcome variable. As compared with the reference group with no or very low caffeine intake, birth weight was 9 g lower in the low caffeine intake group (95% CI −16 to 35), 33 g lower in the moderate caffeine intake group 95% CI 4 to 63), and 69 g lower in the high caffeine intake group (95% CI 35 to 102) , Begg’s test (P = 0.60) or the funnel plot [see Additional file There was no suggestion of publication bias based on Egger’s test  was associated with a 13%, moderate caffeine intake (150 to 349 mg/day) with a 38%, and high caffeine intake (≥350 mg/day) with a 60% higher risk of low birth weight as compared with very low or no caffeine intake. These results suggest a graded relationship between caffeine intake and low birth weight. In a dose–response analysis, each 100-mg/day increment in maternal caffeine intake (about one cup of coffee) was associated with a 13% higher risk for low birth weight. The association persisted across strata defined by various study and participant characteristics.et al. suggested that pregnant women consuming more than 150 mg caffeine per day had a significantly higher risk of low birth weight compared with those with a lower caffeine intake [et al. reported an association between high maternal caffeine intake and a significantly lower offspring’s birth weight and higher risks of having low birth weight and IUGR newborns [Most previous reviews on maternal caffeine intake and low birth weight only qualitatively summarized the available evidence ,16,46. Te intake . This menewborns . HoweverTo date, only one randomized controlled trial has studied the effect of a reduction in caffeine intake during pregnancy on birth weight . This DaOur meta-analysis has several strengths. We searched databases with no language restriction to increase the completeness of studies identification. In addition, we included only prospective studies and, thus, reduced the influence of selection bias, recall bias and reverse causation in our results. Lastly, we not only compared the highest category with the lowest categories but divided maternal caffeine intake into four levels and also conducted a dose–response analysis.et al.’s study [However, our study also has several limitations that have to be considered in the interpretation of our findings. Measurement error in the assessment of caffeine intake may have affected the results. The included studies relied on questionnaires for caffeine assessment. However, in most studies an interviewer-administered questionnaire was used, which may have improved the completeness of their data collection. Furthermore, validation studies have shown that self-reports of major sources of caffeine such as coffee and tea are, in general, reasonably accurate and reliable ,51. Anot’s study ,9 as wel’s study ,56. Anot’s study ,27,35, pet al. [We combined low birth weight, SGA and IUGR in our main analysis. Birth weight is influenced by both duration of gestation and rate of fetal growth. Therefore, low birth weight can result from preterm delivery, insufficient fetal growth or both, whereas SGA and IUGR only reflect fetal growth. Nonetheless, in a recent meta-analysis by Maslova et al. , the autResidual confounding by unmeasured or imperfectly measured covariates should also be considered as a potential limitation of our meta-analysis. A majority of the included studies adjusted for potential confounders rather comprehensively. We only included studies that considered potential confounding by smoking either by adjusting for it in multivariable models or reporting that such adjustment had minimal influence on the results. In addition, most studies adjusted for gestational age, fetal sex and maternal characteristics including age, weight and height, parity, alcohol intake and socio-economic status.Smoking tends to correlate with caffeine intake ,23 and iet al., the observation that higher maternal caffeine intake was associated with higher SGA risk was not affected by adjustment for nausea [Pregnancy symptoms including nausea, vomiting and aversions to smells and taste are more common in healthy pregnancies. Women with healthy pregnancies are more likely to decrease their caffeine consumption in response to pregnancy symptoms  and therr nausea . Furtherr nausea .Thus, the results of the original studies do not suggest that confounding explains the association between caffeine intake and low birth weight. Nevertheless, residual confounding cannot be completely ruled out in observational studies.In addition to methodological limitations of the original studies, publication bias can affect the results of meta-analyses. In our meta-analysis, statistical tests for publication bias or the funnel plot did not suggest publication bias, but this type of bias can never be fully ruled out.We assumed a linear relationship in our dose–response analysis as there was no evidence of departure from linearity. Also, our analysis based on categories of caffeine intake suggested a graded association between caffeine intake and the risk of low birth weight. We acknowledge that in the conduct of a meta-analysis, the use of reported data for categories of intake instead of individual level data may have reduced our power to detect a non-linear association. However, our finding that there appears to be no clear threshold level of intake below which caffeine does not affect birth weight is in concordance with two original studies that examined dose–response relationships using sextiles  or splinThe exact mechanism through which caffeine may impair fetal growth remains unsettled. One of the hypothesized mechanisms is that caffeine increases the release of catecholamines, which may lead to vasoconstriction in the uteroplacental circulation and fetal hypoxia and eventually affect fetal growth and development ,13. IndeThis systematic review and meta-analysis supports the hypothesis that higher maternal caffeine intake during pregnancy is associated with a higher risk of delivering low birth weight infants. In our meta-analysis based on categories of caffeine consumption, the risk for low birth weight increased with increasing levels of caffeine intake. The risk for low birth weight was significantly higher even in the low 50 to 149 mg/day) and moderate (150 to 349 mg/day) caffeine intake groups, as compared with the reference group with no or very low caffeine intake. Our dose–response analysis also suggested a linear association with low birth weight across the range of caffeine intakes. This seems relevant for public health recommendations as it indicates that the risk of low birth weight may be elevated even for caffeine intakes below the recommended maximum limit of the current guidelines for pregnant women . Noneth


The effect of circumstances and exposures early in life on the risk of developing ankylosing spondylitis (AS) is largely unknown. The purpose of this study was to determine whether perinatal characteristics predict development of AS.AS cases  were defined as listed with a diagnosis of AS at least once in the Swedish National Patient Register and registered in the Swedish Medical Birth Register (born ≥1973). Population controls were retrieved from the Swedish Population Register , matched on birth year, sex and county. Odds ratios (OR) for developing AS were determined through conditional logistic regression, with regard to: birth weight, birth order, season of birth, maternal age, gestational length, size for gestational age, type of birth, mode of delivery, congenital malformations, mothers’ country of birth, mothers’ civil status and size of delivery unit.In the univariate analyses statistically significant increases in risk for developing AS were observed for having older siblings . No association was observed for the remainder of analysed exposures, although there was a weak association with birth weight below 3000 g , though not for “low birth weight” <2500 g . The increase in risk associated with having older siblings was consistent in a multivariate analysis adjusting for possible confounders . The direction and magnitude of the point estimates were also consistent in several sensitivity analyses and when stratifying by sex.Having older siblings was associated with an increased risk for developing AS. These results need to be repeated and confirmed in other cohorts.The online version of this article (doi:10.1186/s13075-016-0917-1) contains supplementary material, which is available to authorized users. Ankylosing spondylitis (AS) is a chronic and progressive inflammatory disease with onset of symptoms before the age of 45 in the majority of cases, and an estimated 1.30–1.56 million prevalent cases in Europe . Other cNumber of siblings is often applied as a proxy for exposure to childhood infections and has been shown to affect the risk for developing immune-related diseases . StudiesThe relationship between exposures even earlier in life, such as factors influencing pregnancy and birth, and later development of disease has been established for diabetes and cardiovascular disease but it has also been implicated in several diseases characterised primarily by inflammation or autoimmunity . Low birNo large population-controlled studies have been performed investigating how circumstances and exposures early in life affect the risk of developing AS. The overarching aim of this study was to assess the role of environmental factors, specifically pregnancy and perinatal characteristics, in the pathogenesis of AS, with particular focus on birth order, birth weight and season of birth.This is a case–control study, based on the Swedish national health care and population registers.The Swedish National Patient Register (NPR) was initiated in 1964, as an inpatient register collecting administrative and medical data, including diagnoses registered according to the Swedish version of the International Classification of Diseases (ICD)  codes atThe Swedish population register, managed by Statistics Sweden, contains data on residence, migration and socioeconomic factors for all residents .The Swedish Medical Birth Register (MBR) was initiated in 1973 and includes administrative and medical data related to pregnancy, partum and postpartum neonatal care . It is cThe Prescribed Drug Register contains data on all drugs prescribed in Sweden since July 2005, e.g. date prescribed/dispensed, dose and Anatomical Therapeutic Chemical code (ATC code ). The AnAll the registers include the individuals personal identification number (PIN), given to all residents in Sweden, enabling cross-linking of different registers .In this study the NPR was used to identify the AS cases and to retrieve data on AS-related inflammatory diseases 1973–2009. Matched controls (see below) were obtained from the population register and data on perinatal characteristics from the MBR. Data on pharmacological treatment were retrieved from the Prescribed Drug Register and the ARTIS register. All ICD and ATC codes used are presented in supplementary Table S1  who at least once up until 2009 had a visit listing an ICD code for AS  registered in the NPR. We have previously performed a validation study of the AS diagnoses in the NPR and found good validity, with a positive predictive value of at least 80 % for fulfilling the modified New York criteria and 89–97 % fulfilling any of the commonly used classification criteria for spondyloarthritis (SpA) [For each AS case five controls, matched on birth year, sex and county of residence (at the time of their first SpA diagnosis), were retrieved from the population register. Matching at the time of the first SpA diagnosis, rather than the first AS diagnosis, was chosen as the preferred method of matching since a number of cases were expected to first receive another SpA diagnosis before development and subsequent documentation of structural changes of the sacroiliac joints or spine, resulting in a diagnosis of AS. From the population register we also retrieved data on level of formal education and disposable income in 2008, which was used to compare socioeconomic status between cases and controls.Data on AS-related disease manifestations, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and TNFi were used for a stratification of disease severity for the AS cases in the sensitivity analyses: from the NPR we collected data on all registered visits to a non-primary care physician with an ICD code attributed to some of the AS-related inflammatory diseases  for both cases and controls, from birth and up to 2 years after the first AS diagnosis for the index case (at the latest up until 31 December 2011). A 2-year lag period after the first diagnosis of AS was chosen to include patients diagnosed with IBD and psoriasis as a result of medical investigations initiated at the time of the first AS diagnosis.For the AS cases data on pharmacological treatment, prescribed between 1 January 2011 and 31 December 2011, were obtained from the Prescribed Drug Register for the following csDMARDS: methotrexate and sulphasalazine; and for subcutaneously administered TNFi: etanercept, adalimumab, golimumab and certolizumab pegol. From the ARTIS we obtained data on registered treatment with infliximab for the same time period, since this intravenously administered TNFi is normally not prescribed through a pharmacy and thus not included in the Prescribed Drug Register.Variables associated with birth characteristics were retrieved from the MBR. The variables assessed were: maternal age, mother’s country of birth , mother’s civil status , number of older siblings, season of birth, mode of delivery , type of birth (single/multiple), birth weight, birth length, gestational length, birth weight for gestational age , congeniUnivariate odds ratios (ORs) were computed for the association between exposures (birth characteristics) and the outcome (a diagnosis of AS), by use of conditional logistic regression.Birth weight and birth order were also assessed in a multivariate conditional logistic regression analysis, which also included possible confounders ). Two measures of socioeconomic status (mother’s country of birth and civil status) as well as size of the delivery unit were also included. Season of birth was not entered in the multivariate analysis as the univariate analysis did not reveal any sign of association to development of AS.The univariate and the main multivariate analyses were also stratified by sex and by birth year above or below the median.Four sensitivity analyses, essentially subset analyses, were performed, using the same multivariate model as described above. First, excluding all cases and controls with a diagnosis of psoriasis, anterior uveitis, or IBD before or within 2 years after the first AS diagnosis of the index case (excluding 26 % of the entire study population). Second, restricting the analyses to only include cases treated with methotrexate, sulphasalazine, or TNFi during the last year of data collection (2011), limiting the analyses to a presumably more severe subgroup of AS (excluding 64 % of the entire study population). Third, limiting the analysis only to the cases who had received their AS diagnosis at least once from a specialist in rheumatology or internal medicine (excluding 27 % of the entire study population). Fourth, limiting the analysis only to cases who had received an AS diagnosis at least once in outpatient specialized care 2001–2009 (excluding 7 % of the entire study population). An additional analysis, based on only cases and controls still living in their county of birth at the time point of matching, was also performed to minimize the possible influence of migration between regions with different prevalences of ankylosing spondylitis.th to the 99.5th percentile. Comparison of disposable income was performed using the t test. Comparisons of the proportion of mothers with diabetes, between cases and controls, were performed based on Fisher’s exact test.Level of formal education and disposable income in 2008 were compared between cases and controls. Level of formal education was categorized as ≤9, 10–12 and >12 years of schooling and compared using a chi-square test. Disposable income in 2008 was only assessed for those ≥30 years old in 2008, an age when most individuals are assumed to have finalized their formal education, and in order to avoid extreme outliers we only included the 0.5SAS version 9.3 for Windows  was used for aggregation of the data, and SPSS version 21 for Windows  was used for the statistical analyses.The study was approved by the regional ethics committee in Stockholm, Sweden, 9 September 2011 (number: 2011/29-31/1) and conducted in compliance with the Declaration of Helsinki. Informed consent from individual patients/controls was not required.thpercentile = 20; 75th percentile = 28). Demographics, pharmacological treatment, AS-related inflammatory diseases and level of formal education and disposable income in 2008 are presented in Table We identified 1960 AS cases (59 % men) and 8377 matched population controls, included in the MBR (born in Sweden after 1972). A total of 95 % of the cases had ≥3 matched controls. Median age at inclusion (matched at first SpA diagnosis) was 25 years (25In the univariate analyses a statistically significant association with AS Table  was obseThe main multivariate analysis Fig.  confirmeOverall, the OR for having older siblings was similar in all sensitivity analyses Fig. , to thosIn this study having older siblings was associated with an increased risk of receiving a diagnosis of AS. There was also a weak increase in risk associated with a birth weight <3000 g, which could not be confirmed in our primary stratifications of birth weight. We found no association between, season of birth, type of birth, mode of delivery, congenital malformations, gestational length or maternal age, and later being diagnosed with AS.Birth weight has to our knowledge not been studied as a risk factor for being diagnosed with AS. For IBD, which is associated with AS, one case–control study indicated that cases developing IBD had significantly lower birth weight compared to controls , which iLow birth order was, in a previous study comparing 162 AS cases with their healthy siblings, a risk factor for developing AS . In contSome limitations should be considered. First, misclassification of cases may be a problem when using health care registers for identification. Previous validation studies performed by our group have, however, demonstrated high validity for ICD codes for AS in the Swedish registers . FurtherOur study also has several strengths. First, this is the only study of this research question in AS comparing cases to population controls. Second, it is based on national health care registers, capturing the vast majority of AS cases in Sweden , which rOur results point to environmental factors as possible predictors for development of AS. More specifically, we found that having older siblings increased the risk for a later diagnosis of AS, indicating that factors related to childhood exposure may be of importance in the disease pathogenesis.


Alterations in postprandial metabolism have been described in familial combined hyperlipidemia (FCH); however, their underlying mechanisms are not well characterized. We aimed to identify factors related to the magnitude of postprandial lipemia and apolipoprotein (apo) A-V levels in subjects with FCH.FCH cases (n = 99) were studied using a standardized meal test. Abdominal obesity was assessed using the waist to hip ratio (WHR). A linear regression model was performed to investigate the variables associated with the triglycerides incremental area under the curve (iAUC). Independent associations between metabolic variables and apo A-V iAUC were also investigated in a randomly selected subgroup (n = 44). The study sample was classified according to the presence of fasting hypertriglyceridemia (≥150 mg/dL) and abdominal obesity (WHR ≥0.92 in men and ≥0.85 in women) to explore differences in parameters.2 = 0.29, P < 0.001). The triglycerides iAUC was independently associated with the apo A-V iAUC . Patients with both hypertriglyceridemia and abdominal obesity showed the most robust triglycerides and apo A-V postprandial responses.The fasting apo B-48 levels (r = 0.404), and the WHR (r = 0.359) were independent factors contributing to the triglycerides iAUC (rIn patients with FCH the fasting apo B-48 level is the main factor associated with postprandial lipemia. Abdominal obesity also contributes to the magnitude of the postprandial response.The triglycerides postprandial increment is the principal factor associated with the apo A-V postprandial response. Postprandial lipemia refers to the increment of triglycerides rich lipoproteins (TRL) in plasma after a meal. This process is associated with an increase in very low density lipoproteins (VLDL) that are transformed to low density lipoproteins (LDL) and delivered to the arterial wall, a decrease of high-density lipoprotein (HDL) particle number and function, and production of small-dense LDL. This unfavorable lipid profile increases cardiovascular disease (CVD) risk . PostpraFasting triglycerides concentration represents the main determinant of postprandial lipemia, explaining around 30% of the variance . In seleRecent studies have suggested a role for apo A-V in modulating triglycerides metabolism . FirstlyFamilial combined hyperlipidemia (FCH) is the most common genetic form of dyslipidemia . It is aIn this study we explored the factors associated with postprandial lipemia in patients with FCH and whether the metabolic phenotype alters the magnitude of this phenomenon. We first analyzed the determinants of postprandial triglycerides incremental area under the curve (iAUC). Subsequently, in a randomly selected subgroup, we investigated factors associated with fasting and postprandial Apo A-V. Finally, we classified participants according to the presence of fasting hypertriglyceridemia (HTG) and increased waist to hip ratio (WHR) in order to evaluate if the metabolic phenotype modulated the magnitude and time-sequence of the triglycerides iAUC.2, alcohol consumption >10 g/day in women and >20 g/day in men, or currently taking medications known to affect lipid metabolism. Individuals with other primary or secondary dyslipidemias were also excluded.The study population was selected from an out-patient cohort of families with FCH identified at the Instituto Nacional de Ciencias Medicas y Nutricion in Mexico City. None of the subjects were taking lipid-lowering therapy mainly because they were newly diagnosed. FCH was diagnosed using the following criteria: 1) LDL-cholesterol and/or triglycerides concentrations >160 mg/dL and >150 mg/dL, respectively; 2) at least one first-degree relative with hyperlipidemia with a different lipid phenotype, and 3) a concentration of apo B > the 90th percentile for the Mexican population  –14. All The Comite de Etica en Investigacion del Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran approved the protocol and informed consent was obtained from all subjects.Subjects completed a comprehensive medical evaluation, including a history and physical examination. Anthropometric measurements including height, weight, waist, and hip circumference, systolic and diastolic blood pressures were measured following standardized procedures.Subjects were asked to attend after a 12-hour fasting period, and a standardized meal was provided. Blood samples were then obtained at 0 (fasting), 3, 4, 6, and 8 hours after meal ingestion . The meaBlood samples were collected in EDTA-containing tubes. Levels of triglycerides, total cholesterol, HDL-cholesterol (HDL-c), glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyltransferase (GGT) were measured by automated enzymatic assays . LDL-cholesterol (LDL-c) was calculated by the Friedewald formula  when theThe iAUC over the 8-hour period was calculated using the trapezoidal method by subtracting the fasting concentration from the total AUC. To evaluate insulin sensitivity the homeostasis model assessment (HOMA-IR) index and the Matsuda index were calculated –19.Data were examined for normality with the Shapiro-Wilk test. Continuous variables are reported as mean ± SD (standard deviation) or median and [interquartile range (IQR)] as appropriate. Categorical variables are reported as frequencies and percentages. Friedman tests were performed to examine the triglycerides, apo B-48, and apo A-V postprandial responses. Following logarithmic transformation of non-normal distributed variables, Pearson correlations were calculated and stepwise multiple linear regression models were constructed to investigate the independent predictors of the iAUC of triglycerides and apo A-V. In the first model, the dependent variable was the triglycerides iAUC and the independent variables were the fasting apo B-48, fasting triglycerides, time of triglycerides peak, WHR, HOMA-IR, and the apo B. In the second model, the dependent variable was the apo A-V iAUC. This model included the triglycerides iAUC, apo B-48 iAUC, fasting triglycerides, apo B, and HDL-c as independent variables.The population was then classified into four groups according to the presence or absence of HTG  and abdominal obesity . One way ANOVA or Kruskal Wallis tests were performed to examine differences between these groups as appropriate. If significance was achieved  comparisons between individual groups were performed with independent T test or Mann–Whitney U test as appropriate. Statistical analyses were performed using SPSS software version 19.0 . A P value <0.05 (two tailed) was considered statistically significant.2), and had a mean waist circumference of 89.1 ± 10.6 cm. The baseline characteristics of the randomly selected subgroup (n = 44) used for apo A-V and apo B-48 analysis were similar in comparison with the whole cohort , presence of undiagnosed diabetes (n = 1), and an elevated fasting triglycerides concentration (n = 1). The characteristics of the 99 individuals participating in the study are summarized in Table After the meal challenge, plasma triglycerides, apo B-48, and apo A-V concentrations increased significantly P < 0.001) , representing the chylomicrons increase in response to the meal ingestion.The fasting and 8-hour apo A-V/triglycerides ratio was estimated to evaluate the change in this index associated with the chylomicrons response after ingestion of the meal. We did not find a significant change in this index comparing the fasting state and 8 hours after ingestion of the meal .The triglycerides iAUC showed a significant correlation with the fasting apo B-48 and the fasting triglycerides concentrations . In addition, significant positive correlations were found between the triglycerides iAUC and the time of triglycerides peak , WHR , apo B , BMI , and HOMA-IR . A significant negative correlation was identified between Matsuda index and the triglycerides iAUC .Despite a positive correlation between the triglycerides iAUC and the apo B-48 iAUC , we did not find significant correlations between the apo B-48 iAUC and the studied variables.The linear regression analysis identified the fasting apo B-48 levels (r = 0.40), and the WHR (r = 0.35) as independent parameters determining the triglycerides iAUC, explaining 29% of the variability. The model also included the fasting triglycerides concentration, time of triglycerides peak, HOMA-IR, and the apo B levels, none of these parameters demonstrated an independent association with the triglycerides iAUC  and apo B levels .The apo A-V iAUC showed significant associations with the triglycerides iAUC , apo B levels , apo B-48 iAUC , and fasting triglycerides levels . A negative correlation between the apo A-V iAUC and HDL-c was also found .In the linear regression model, the only variable independently associated with the apo A-V iAUC was the triglycerides iAUC, explaining 54.4% of the variability in this variable (P < 0.001). This model also included the apo B-48 iAUC, fasting triglycerides, apo B, and HDL-c levels as independent variables. When the triglycerides iAUC was removed from this model, the apo B-48 iAUC, apo B, and HDL-c were associated with the postprandial apo A-V response, explaining 51.1% of the variability in this parameter.Individuals were classified in four groups according to the level of fasting triglycerides and the median WHR as follows: 1) HTG (≥150 mg/dL) with abdominal obesity (WHR ≥0.92 in men and ≥0.85 in women), 2) HTG without abdominal obesity, 3) normotriglyceridemia (NTG) (<150 mg/dl) with abdominal obesity, and 4) NTG without abdominal obesity. The characteristics of these groups are shown in Table Individuals with fasting HTG and abdominal obesity, showed the highest triglycerides iAUC, and the time to triglycerides peak concentration was later (median 5 hours) than in the other groups. In this group apo B-48 peak concentrations were also higher. Triglycerides peak level was higher in the groups with fasting HTG in comparison with the groups with normal fasting triglycerides concentration. The apo B-48 iAUC showed a tendency to be higher in groups with fasting hypertriglyceridemia.The highest apo A-V iAUC and peak concentrations were observed in the HTG with abdominal obesity group, followed by the group with HTG without abdominal obesity. The group without any of the abnormalities showed the shortest time to peak apo A-V levels. In contrast, the group with both HTG and abdominal obesity showed a later peak. These results are summarized in Figure The lipoproteins and mechanisms that modulate postprandial lipemia in patients with FCH are not well understood. We studied a cohort of patients with FCH to determine factors related to postprandial lipemia. Our results show that the magnitude of the triglycerides iAUC is determined by the fasting apo B-48 concentration and the WHR. In our second linear regression model the postprandial apo A-V levels were only associated with the triglycerides iAUC. When the study population was classified according to the fasting triglycerides level and the WHR, the most robust postprandial triglycerides response was observed in the group with fasting HTG and abdominal obesity.These results indicate that the magnitude of the postprandial lipemia in patients with FCH is determined by the fasting apo B-48 concentration and potentiated by the presence of abdominal obesity. However, the linear regression model explained only a modest proportion of the variability in postprandial lipemia; therefore, additional variables related to this phenomenon may be involved.Interestingly, the apo B-48 postprandial response, reflecting the chylomicrons rise after the meal, was not independently associated with abdominal obesity or fasting hypertriglyceridemia. This result indicates that in patients with FCH the chylomicron response is not determined by the same parameters that influence the postprandial triglycerides iAUC .In contrast to our results, other studies including individuals with diverse cardiovascular risk have reported that fasting triglycerides levels is the major determinant of postprandial lipemia , 6, 20. The relationship between abdominal obesity and postprandial lipemic response is less clear. Abdominal adiposity may be associated with liver fat deposition, a driving force for the overproduction of VLDL . We founIn patients with FCH the postprandial lipid response was aggravated by abdominal obesity. A feasible mechanism for explaining our results is the oversaturation and competition of chylomicrons and VLDL particles for the same removal pathways . This coAPOAV have been associated with increased fasting triglycerides concentrations [A novel finding of our report is the analysis of the fasting and postprandial apo A-V response. Apo A-V postprandial levels were mainly associated with the postprandial triglycerides iAUC. Apo A-V is produced by the liver and is a component of VLDL and HDL lipoprotein fractions . It is ptrations . In thistrations . In the trations , 26.Our study has limitations. The cross-sectional design only suggests associations and not causality. In addition, we did not use DEXA or imaging studies to measure fat mass and visceral adipose tissue volume. This would have allowed more precise quantification of abdominal obesity; however, the WHR is a validated marker of visceral tissue accumulation . Also, tIn conclusion, in individuals with FCH fasting apo B-48 concentration is the main factor associated with the magnitude of postprandial lipemia. This response is potentiated by abdominal obesity. Finally, the Apo A-V postprandial levels are associated with the postprandial triglycerides increment.


In obstetrics, effectiveness and cost-effectiveness studies often present several specific outcomes with likely contradicting results and may not reflect what is important for women. A birth-specific outcome measure that combines the core domains into one utility score would solve this problem. The aim of this study was to investigate which domains are most relevant for women’s overall experience of labor and birth and should be included in such a measure.A sequential mixed-method design with three steps was applied. First, the domains were identified by literature review and online focus groups consisting of pregnant women, women who recently gave birth, and their partners. Second, in a prioritizing task, women who recently gave birth and professionals  selected and ranked their top seven domains. Third, the domains that were most frequently selected and had the highest ranking scores determined the basis for a consensus discussion with experts, whereby the definitive list of domains was formed.In the first step, 34 birth-specific domains were identified, which cover domains regarding the caregivers, intrapersonal aspects of the mother, partner support, and contextual and medical aspects of birth. Based on the prioritizing task results (step 2) of 96 women and 89 professionals, this list was reduced to 14 most relevant domains. In a consensus discussion, the final seven domains were selected by combining several of the 14 remaining domains and giving priority to the domains indicated to be relevant by mothers. The seven definite domains were: 1) availability of competent health professionals; 2) health professionals’ support; 3) provision of information; 4) health professionals’ response to needs and requests; 5) feelings of safety; 6) worries about the child’s health; and 7) experienced duration until the first contact with the child.The experienced availability and quality of received care, concerns about safety and the baby’s health, and first contact with the baby are regarded as key aspects for a mother’s overall birth experience. Therefore, these domains are considered to be the most crucial for inclusion in a birth-specific outcome measure. In medical research, innovative health care interventions are constantly evaluated and compared with routine care. The evidence derived from these effectiveness and cost-effectiveness aims to provide input for medical decision making for patient care . The preCurrently, these indicators are typically considered separately; one indicator is considered as a primary outcome measure and several others are considered as secondary outcome measures. These different outcomes may be contradictory, e.g., the amount of pain perceived during labor might be inconsistent with the quality of the care received during labor as experienced by the mother. Therefore, a composite outcome measure that reflects the core domains of the labor and birth based on the women’s experience and combines these domains into one utility score would solve the problem of separate outcome presentation . A prefeIn existing multidimensional self-report questionnaires for obstetric outcomes, the differences in the subscales’ extent of contribution to the overall experience of labor and birth are not considered ,13-15. BBefore a new composite outcome measure can be developed, it is necessary to investigate which domains of labor and birth are most relevant for women’s overall experience of labor and birth. Therefore, as a first step in this development process in the present study, we reported results for the following research questions: First, what are the birth-specific domains that play a role in women’s experience of labor and birth? Second, what are the birth-specific domains (seven at most) regarded to be most relevant for women’s experience of the process of labor and birth?The present study holds a mixed-methods design and consists of three steps . In the The Medical Ethics Committee of the Leiden University Medical Centre approved this study.Literature search The aim of the scoping review search was to investigate existing literature concerning birth experiences to gain a comprehensive overview of likely domains. The term “scoping review” refers to an approach in which a rapid search is conducted to map evidence in a high-volume research area. Using this method, the depth and broadness of evidence coverage vary depending on the search aim. Because of the explorative nature of our research questions, the scope of our review was broad instead of a review of in-depth evidence [evidence ,21.Three electronic databases  were systematically searched for peer-reviewed articles in March 2011. For the search strategy, three search groups were combined with the Boolean operator AND; first, a group of search terms for obstetrics, labor, and birth; second, a group of search terms for outcomes and experiences; and third, search terms for broad study outcomes, such as “outcome and process assessment” or “questionnaire”. For each of the three groups of search terms, index terms specific for each database (such as MESH terms in PubMed) were combined with free-text words for searching in the title or in the title and abstract. The complete search strategy is presented in the Additional file Selection of studies All retrieved articles were evaluated for eligibility based on the title and abstract. If this evaluation did not provide adequate certainty about inclusion, the article was evaluated based on its full-text. Articles were eligible for inclusion in the study if the articles eithera. studied one or more domains in a specific population or compared the domain(s) between different populations,b. identified one or more domains,c. used one or more domains as outcome measure,d. studied the relationship between different domains, ore. evaluated or developed a questionnaire that measures one or more domains.As a domain, we regarded all experiences or emotions of the mother related to the process of labor and birth or to the period shortly after birth (maximum of one week). Excluded were articles that present systematic reviews, except for reviews that aim to inventory domains on birth experience. Additionally, case reports were excluded because we included individual experiences, to a large extent, by the focus group data. Also excluded were articles that studied the outcomes of specific obstetric interventions, which detracted from generalizability , and articles that were not written in English, German, or Dutch.Data extraction and analyses of the literature search For each included article, the key terms describing the domains that are investigated in the article were inventoried. Depending on the type of study, this inventory could be variables, for example, that determine group differences, outcome variables used, results from qualitative data, or questionnaire subscale. A data-driven thematic analysis of the data extracted from the included articles was performed [erformed . First, Recruitment of focus groups participants and experts Three online focus groups were convened, one for pregnant women, one for women who recently gave birth, and one for partners of the latter group. The participants were recruited between September and November 2011. The participants had to be at least 18 years, conversant in Dutch, and meet one of the following criteria: be in the third trimester of pregnancy, have recently (within 12 months) given birth, or be a partner of the latter group of women. The participants were recruited from the Department of Obstetrics and Gynecology of a Dutch academic medical center, through primary-care midwifery practices, and through calls on websites for this target population. The focus group data were supplemented with keywords that were presented by midwives and obstetricians who were part of the research team network.Procedure of focus groups and experts data gathering After providing their written informed consents, the participants received their log-in data for the online forum and registered using a self-chosen username. The respondents received an information leaflet that provided the aim of the study, the date, and the time of the focus groups. The respondents were instructed to log in at least once, but they were encouraged to log in more often and to react to each other’s comments. The online focus groups were structured according to two questions that were slightly adapted for the three different groups of respondents. First, the participants were asked to introduce themselves and to provide key aspects concerning labor and birth. After 24 hours, the second question was posed to the forum, which asked participants to explain which domains were predominant for their (or their partners’) overall experience of labor and birth. The moderator (E.v.d.A.-v.M.) occasionally summarized the answers and encouraged the participants to clarify their keywords and to react to each other’s answers.What are the most important aspects concerning mother and child that should be included in a composite outcome measure on birth experiences?” For the obstetricians, this question was part of a larger questionnaire from another study that encompassed 90 hospitals in the Netherlands, accompanied with the request that the head of the gynecology department or a colleague who specialized in obstetrics complete the form. The midwives received this question by e-mail.The professionals’ opinions were assessed by means of an open-ended question: “Professionals’ opinions were not gathered during focus groups because the professionals were very familiar with the topic and they are accustomed to stating their opinions; therefore, it was considered less necessary to stimulate reflection during group discussion, as is done in focus groups.Analysis of focus group data and expert opinions The analysis of the focus group and expert opinion data followed a purpose-driven approach that aimed to distinguish as many different aspects of labor and birth as possible. First, the transcripts of each focus group were open-coded. Second, axial coding was performed. Within this process of re-rereading, the codes were refined, reduced, and related to each other. Third, the obtained codes were categorized into themes that covered related aspects of labor and birth, which resulted in the list of the domains [ domains ,24. One  domains .The domains derived from the literature search and the focus group data were synthesized into one list of domains. For each domain, a definition was formulated, discussed, and rephrased in the research team until a consensus was reached.To be included in the sample of women who recently gave birth, women had to have given birth between October 2012 and February 2013 and be conversant in Dutch. There was no restriction on any obstetric characteristic because we aimed to achieve diversity in the sample. Women were recruited via flyers at obstetric outpatient clinics and primary-care midwifery practices, as well as calls on the intranet and the official website of a Dutch academic medical center, information on websites for pregnant women, and Twitter and Facebook accounts of midwives.The obstetricians and midwives were recruited via the personal network of the research team members. The link to the online questionnaire was e-mailed to 86 midwives or primary-care midwifery practices and to 56 obstetricians, accompanied with the request to complete the questionnaire and to forward the e-mail to other professionals who might be interested. Twenty-one researchers working in the field of obstetrics in the Netherlands were recruited via a personal e-mail invitation.not relevant, 1 = slightly relevant, 2 = relevant, 3 = very relevant, 4 = extremely relevant). This relevance score was dichotomized into “non-substantial”  and “substantial” (scores 3 and 4). We chose to not include the middle category “relevant” in the categorization of “substantial” domains because based on the methods we used for generating this list of 34 domains, we expected all of the domains to be relevant. However, to distinguish within this list of relevant domains, we believed that the domains should be of extra importance.During January and February 2013, the online questionnaire was distributed by e-mail to the participants. In this online questionnaire, 34 identified domains with their definitions were presented. The appraisal of the relevance of the domains contained three parts. First, to become familiar with the domains and their definition, the domains were presented singly to the respondent. The respondent was asked to rate the perceived relevance for each domain using a 5-point scale , facts about the most recent birth , and demographic and work characteristics . For the professionals, additional questions on gender, profession, and years of work experience were asked to gain insight into the characteristics of the sample.Based on the data of the prioritizing task, a list of the most important domains was identified. For this list, the seven domains with the highest proportion of the top seven selection (part 2) and the seven domains with the highest mean ranking score were included (part 3). This analysis was done separately for the two datasets, i.e., the sample of women who recently gave birth and the sample of professionals.All statistical analyses were performed using IBM SPSS 20.0  .In the last step, an expert meeting with a consensus discussion was held to reduce the list of most important domains, derived in step two, to a maximum of seven domains. To achieve this aim, the domains were combined or reduced. All of the decisions made by the experts had to guarantee that the final domains fulfilled the following three requirements:1. The domains are clearly distinguished and independent of each other.2. Each domain must be measurable by self-reports of the mother.3. Each domain must be applicable to all types of deliveries, regardless of place and type of labor, e.g., home versus outpatient clinic versus hospital, and vaginal versus caesarean section.Furthermore, we decided that the results of the sample of women who recently gave birth were leading for the decisions made during the reduction process. The reason for this choice was that the instrument to be developed aimed to measure the experience of the women who gave birth and thus predominantly should present the domains they regard as important. However, overall, the final list of domains must be supported by the data of the professionals.For the expert meeting, we invited midwives, obstetricians, and researchers in the fields of obstetrics, health economics, or clinimetrics. The experts were recruited from the researchers’ personal network and they were members of the research team.A total of 2,060 titles were identified by the literature search: 959 in Pubmed, 828 in Web of Science, and 273 in PsycINFO. After eliminating 211 duplicates and adding five relevant articles by the research team, 1854 articles were reviewed for inclusion, of which 170 articles met the inclusion criteria. Of these 170 included articles, 70 fell into inclusion category a (studied one or more birth-specific domains in a specific population or compared the birth-specific domain(s) between different populations); 11 fell into category b (identified one or more birth-specific domains), 15 fell into category c (used one or more birth-specific domains as outcome measure), 43 fell into category d (studied the relationship between different birth-specific domains), and 31 fell into category e . We regarded the data to be saturated because each domain identified in the literature was derived from at least two papers, but in the majority of cases by more than four papers. Because of the extent of the list of included articles, the references are not included in this paper but can be provided from the corresponding author.For the online focus groups, 34 participants registered, of whom 29 participants in fact participated: nine pregnant women, 13 women who recently gave birth, and seven partners. Their mean age was 32.4 years (SD = 3.6). Fifty-five obstetricians and midwives responded to the call to name aspects of labor and birth that are crucial to the evaluation by women. In total, 55 professionals provided key terms and their opinions concerning the most important aspects of birth.transfer between medical staff, freedom of movement during labor, duration of labor and birth, compliance with expectations) and two domains were derived solely from the focus group and expert data .In total, 34 domains were identified Table . Of thescompetence of caregivers and treatment by caregivers), the role of the partner (such as support of the mother by her partner), more intrapersonal domains of the mother on the experience of labor (such as fear of the mother during labor and feelings of control of the mother over the situation), domains regarding facts on the environment and method of the birth and interventions (such as place of birth and pain relief), and other domains (such as first contact with the child).The list of domains comprises the domains regarding caregivers  , slightly more primipara (54.2% versus 47.5%), slightly fewer home births (11.5% versus 17.1%), fewer planned caesarean sections (2.1% versus 7.6%), but more emergency caesarean sections (17.7% versus 9.2%), and more pain medication by epidural anesthesia (30.2% versus 15.9%). The mean age when giving birth was similar, i.e., 32.7 years in our sample and 32.1 years in The Netherlands in 2010 .In the group of professionals, 89 persons completed the questionnaire. On average, they were 39.5 years old and had a mean work experience of 13 years. In this sample, 96% was female and 56% were midwives, 23% obstetricians or residents in obstetrics, and the remaining respondents were researchers, teachers, or had other professions.stress during labor) and the role of their partner. The professionals regarded domains concerning stress of the mothers and the support of the mother by the partner as more important than their own role . Furthermore, it is notable that in both samples, the domains concerning the course of labor (such as pain perception and duration of labor) and medical and environmental aspects  are not represented in the total list of most important domains.In the prioritizing task, 14 domains were selected as most relevant  availability of competent health professionals; 2) support by health professionals; 3) provision of clear information by health professionals; 4) health professionals’ response to the mother’s needs and requests; 5) feelings of safety; 6) worries about the child’s health state; and 7) experienced duration until the first contact with the child.The following decisions and rationale underlie this final list:feelings of safety), 30 , and 33 (duration until the first contact with the child) were included in the definite list of domains because they fulfill all requirements.• Domains 20  and 10  were combined because the availability of caregivers is regarded to be only valuable in combination with their competence; for example, the presence of midwives or doctors in training might not always be perceived as positive by women in labor.• Domains 1  and 9  were combined because these were regarded to be not independent of each other.• Domains 2  was deleted from the list because a subjective measurement by self-report of the mother was regarded to be not likely.• Domain 12 (support of the mother by her partner), 17 (trust of the mother in a good course of labor), and 19 (stress of the mother during labor) were removed by the experts because they did not stand out in the prioritizing results of the sample of women who recently gave birth.• Domains 13 (self-confidence of the mother) was removed from the final list because only a small group of women (15%) chose this domain in their top seven; therefore, the experts regarded this domain to be inferior to the other domains.• Domain 15  was deleted because it was regarded to overlap with domain 20 (feelings of safety).• Domain 31  were combined into one extra domain concerning the caregivers’ response to the mothers’ needs and requests because it is regarded to be a crucial component of personalized care.• Domains 6, 7, and 8 on personalized care  availability of competent health professionals; 2) health professionals’ support; 3) provision of clear information by health professionals; 4) health professionals’ response to the mother’s needs and requests; 5) feelings of safety; 6) worries concerning the child’s health state; and 7) experienced duration until the first contact with the child.Interestingly, the results of the prioritizing task indicate that domains regarding the health professionals’ behavior and attitude, as well as domains regarding the mothers’ feelings of confidence and safety prevail over domains regarding the course of labor and the medical and the environmental aspects of the birth. These findings are consistent with the results of a systematic review of predictors for childbirth experience . Hodnettinvolvement of parents in decision making (domain 6) did not dominate in the top 7 selection, especially in the sample of women who recently gave birth. In contrast, in the results of the review of Hodnett and colleagues and also in various birth experience scales, involvement in decision making plays an important role in the evaluation of the birth experience [involvement of parents in decision making (domain 6), provision of clear information (domain 5), considering wishes (domain 7), and considering specifics on the pregnancy or previous labor experience (domain 8). In the prioritizing task, domains that are similar might have competed with each other. Respondents might have nominated seven different and independent domains, rather than domains that overlapped in their meaning, to obtain a top 7 selection that represents as many different aspects as possible. Thus, the domains on personalized care might have oppressed each other, and none of them clearly stood out in the selection and ranking scores, except for the provision of clear information (domain 5). These considerations were discussed in the expert meeting. The group concluded that the following two key components of shared decision making should be reflected in the final list of domains: 1) informing the patient and 2) personalizing care based on the individual needs and wishes [Another conspicuous result of the prioritizing task is that the domain g domain  did not perience -13,28,29d wishes ,31. TherThe bottom-up approach to inventory the domains was a strength in this study. A mixed-methods approach was used to derive a comprehensive list of domains, and both women’s and professionals’ experiences of labor and birth strongly contributed to the result.A possible concern regarding the validity of the results for the prioritizing task arises from the composition of our sample of women who recently gave birth. A selection bias might have occurred because women with a higher educational degree were overrepresented, as well as respondents of Dutch origin. In future studies, and especially in the determination of utility values for the seven definite selected domains, it is important to improve the participation of lower educated women and immigrant women.Furthermore, the validity of our results outside The Netherlands should be discussed. Hodnett and colleagues concluded that in their review, the results of the experience of childbirth are consistent regardless of the country . The obsRegarding the generalizability within the Dutch setting, we note that our results derived from a single setting study. The replication of the study in the same cultural context, but with a larger sample size, would strengthen the validity of the results.In the present study, we investigated which domains of labor and birth are regarded to be most relevant for women’s overall experience of labor and birth and we derived a final selection of seven domains. As explained in the introduction of this study, a composite outcome measure is needed for the cost-effectiveness studies in obstetrics . The resIn addition to using the results for developing a utility measure, the results of this study are of relevance for obstetric professionals and policy makers. The prioritizing results showed that there are several discrepancies in what women who recently gave birth and professionals regard to be important for the overall evaluation of the experience of labor and birth. Based on the results of part two of our study, it might be concluded that women regard the attendance and support of health professionals to be more important than what the professionals think it is for the evaluation of the labor. This fact underscores the importance of the psychosocial portion of the care provided in obstetrics. In future research, these incongruences need to be further studied, as well as their implications for the fulfillment of expectations women have for obstetric care. It is known that previous expectations influence the evaluation of a birth . Thus, tBased on a sequential mixed-method design that combined literature review with results of focus groups with women and their partners and with the quantitative data of women and professionals, a list of seven domains was derived that considered the key aspects for a mother’s overall experience of labor and birth. This list covers aspects of the caregivers’ competence, support, and communication, the mother’s feelings of safety, fulfilment of her needs, her worries concerning the child’s health and the experienced duration until the first contact with the baby. The results of our study are regarded as a useful contribution to health technology assessment and to research concerning patient-oriented health in the field of obstetrics. In the future, the list of seven domains that was derived from our study might be used as input for developing a birth-specific utility index and a checklist for caregivers in obstetrics to promote a positive labor and birth experience for women, given the medical circumstances.The Medical Ethics Committee of the Leiden University Medical Centre gave approval for this study.QALY: Quality Adjusted Life Year.All authors declare that they have no competing interests.FG contributed to the conception and design of the study, the acquisition of data, the analysis and interpretation of the data, and drafted the article. LF contributed to the conception and design of the study, the acquisition of data, and interpretation of the data and provided critical revision of the article. MR contributed to the conception and design of the study, the acquisition of data, and interpretation of the data and provided critical revision of the article. JM contributed to the conception and design of the study, interpretation of the data and provided critical revision of the article. KB contributed to the conception and design of the study, interpretation of the data and provided critical revision of the article. AS contributed to the conception and design of the study, interpretation of the data and provided critical revision of the article. EvdA-vM contributed to the conception and design of the study, the acquisition of data, the analysis and interpretation of the data, and provided critical revision of the article. All of the authors provided final approval of the version to be published.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/14/147/prepubSearch strategy PubMed, Search strategy Web of Science, Search strategy PsychINFO.Click here for file


Studies have shown that shorter women are at a greater risk of preterm birth. In light of these previous findings, we aimed to assess whether maternal height was associated with gestational age in a cohort of children born at term.Subjects were a control cohort of 294 children of New Zealand European ethnicity, high socioeconomic status, naturally conceived, born appropriate-for-gestational-age of singleton pregnancies at 37–41 weeks of gestation. Gestational age was determined by ultrasound scans performed <20 weeks. Maternal and paternal heights were measured using a Harpenden stadiometer. Associations with maternal height were assessed using linear regression mixed models, accounting for infant's gender, birth order, maternal age, and paternal height, with family number added as a random factor.Mothers were 167.5 (SD=6.2) cm tall (range 151.4–183.0 cm). Increasing maternal height was associated with longer gestation (p=0.002). Stratified analyses showed that the main effect appears to occur among shorter mothers , who experienced gestation that was ~0.6 weeks shorter than that of mothers 165–170 cm (p=0.001) and >170 cm (p=0.0002) tall . There was also a progressive increase in birth weight standard deviation scores with increasing maternal height (p<0.0001). Paternal height was not associated with study outcomes.This study shows that maternal height is positively associated with gestational length across the term window. An association between shorter mothers and preterm birth has been previously shown. We have extended this observation showing that maternal short stature is associated with shorter pregnancies within the term window. The breakdown of term pregnancies into early term (37 0/7 – 38 6/7 weeks of gestation), full term (39 0/7 – 40 6/7 weeks), and late term (41 0/7 – 41 6/7 weeks) has recently been proposed, in light of differences in neonatal morbidity and mortality as well as in neurocognitive outcomes later in life.Maternal stature seems to be a factor determining offspring outcomes, with proposed underpinning mechanisms including socioeconomic factors, undernutrition in utero, and anatomical constraints on pelvis during birth. In our study, socioeconomic factors were not at play in light of the homogeneity of our cohort. Lastly, our findings also support the lack of a paternal height effect on length of gestation.


Manganese (Mn) is an essential trace element for humans and animals, but excess intake of Mn can lead to adverse developmental outcome. Few studies have investigated the effects of deficiency or excess of Mn on the human foetus. In this study, we assessed the quantitative relationship between maternal blood Mn and birth weight of a newborn.We performed analysis on 331 full-term, live birth singleton mother-infant pairs enrolled from July 2007 to December 2009 in the Mother and Children’s Environmental Health (MOCEH) study in Korea. A questionnaire on general characteristics, a review of medical records, and maternal whole blood Mn analysis were performed at full-term pregnancy. We evaluated the relationship between maternal blood level of Mn and the birth outcome using logistic regression and generalised additive model.The mean Mn concentration in whole maternal blood was 22.5 μg/L. We found a curvilinear relationship between maternal blood Mn and birth weight after adjusting for potential confounders. Birth weight peaked at the maternal blood Mn level of 30 and 35 μg/L. An increased probability of birth weight below 3000 g was observed at both below 16.9 μg/L  and above 26.9 μg/L of maternal blood Mn level .Our study found that both extreme level of maternal Mn level was associated with lower birth weight outcome in a nonlinear fashion. Manganese (Mn) is one of the essential nutrients for humans and animals . It is rPregnant women and infants typically show an increase in blood Mn level, which becomes more prominent in the later phase of pregnancy . High MnMn-related maternal and developmental toxicities have been observed in studies of experimental animals, including reduced foetal body weight and high Mn level ,13. Few This analysis was conducted on a community-based birth cohort study, the Mothers and Children’s Environmental Health (MOCEH) study. MOCEH is designed to investigate the effects of pregnant women’s environmental exposure on foetal and postnatal growth and development in three centres; Seoul, Cheonan, and Ulsan, Republic of Korea . Among 9This study protocol was approved by the institutional review boards of Ewha Womans University, Dankook University Hospital, and Ulsan University Hospital. Informed consent was obtained from all the study participants at the time of recruitment.Data were collected by a questionnaire and from each woman’s medical records before 20 weeks of gestation by a trained nurse at the outpatient clinic and at the time of visit for delivery. The questionnaire consisted of socio-demographic information such as mailing address, age, height, weight, occupation, education, and income; pre-pregnancy alcohol consumption; smoking history; complications of the current pregnancy; and the subject’s biological, medical, and obstetric history. At delivery, trained nurses measured birth weight using a digital scale.Medical records were reviewed to collect information on maternal pre-pregnancy weight, maternal height, gestational age, parity information, delivery mode, infant sex and birth weight, presence of preterm birth or low birth weight, delivery date, maternal term weight and presence of intrapartum complications including premature rupture of membranes, cephalopelvic disproportion, dystocia, breech presentation or other abnormal position, placenta abruption, placenta previa, meconium aspiration syndrome, foetal asphyxia, obstetrical haemorrhage, precipitating labour, cord prolapse or eclampsia during labour, fever, and use of anaesthetics.et al. [Maternal venous blood samples (10 ml) were obtained at the visit for delivery and stored at -70°C until it was transferred to the laboratory at the Neodin Medical Institute for analysis. Whole blood Mn level was measured by graphite furnace atomic absorption spectrophotometry . The laboratory analyses were conducted using standardised quality-control procedures from the German External Quality Assessment Scheme and Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine of the University of Erlangen-Nuremberg as described by Kim et al. . The relThe distribution of maternal blood Mn was slightly skewed to the right (skewness = 1.3), but the distribution was close to Gaussian except for outliers above the 99th percentile value. Therefore, we did not transform it to a log scale. Student’s t-test or ANOVA was performed for unadjusted group differences in maternal blood Mn and birth weight. We assessed the association between maternal Mn level and birth weight by simple regression analysis and then by multiple regression analysis using a second degree polynomial function after adjusting for potential confounders , which were determined from previous studies ,15,18,19p value of < 0.05.Multiple logistic regression was used to assess the relationship between maternal blood Mn and the birth outcome after adjusting for the potential confounders. We categorised the birth weight variable as binary data: lower than 3000 g (which represented less than 20 percentile among the study population) or equal or more than 3000 g. Non-linear relationships were examined by a generalised additive model (GAM) after controlling for potential confounders. Statistical analyses were performed using SAS 9.3 software  and R software (R version 3.0.1). Statistical significance was determined using a The arithmetic mean (SD) of blood Mn concentration in this study population was 22.5 (7.2) μg/L, ranging from 8.5 to 58.6 μg/L, and the median was 21.5 μg/L. Mean infant birth weight was 3303.9 (367.6) g, and mean maternal age was 30.3 (3.6) years. The gestational age and maternal term weight were significantly associated with birth weight, but only gestational age was associated with maternal blood Mn in borderline level of significance (p = 0.067)  after controlling for possible confounders including infant sex, gestational age, maternal education, maternal parity, maternal term weight, maternal income, and maternal age Table .Table We obtained consistent results with the generalised additive model, showing that low and high levels of Mn were associated with birth weight below 3000 g. The birth weight gradually increased up to level of 30 μg/L Mn, then after a peak between 30 and 35 μg/L, decreased at over 35 μg/L level Figure .The results of our multicentre cohort study indicated that both low and high blood Mn level of pregnant women is associated with birth weight below 3000 g of infants. We further identified a curvilinear relationship between maternal blood Mn level and infant birth weight, in accordance with previous report .et al.[It shows that a high level of blood Mn is associated with lower birth weight in full-term infants. A high maternal Mn level, over 36 μg/L, was borderline significantly associated with birth weight below 3000 g although the relationship between high Mn level and lower birth weight in our study population was rather weak. The report of Zota et al. found a et al., they foet al., northeret al.,15,22.Another study conducted in Southwest Quebec also tested the hypothesis of an inverted U-shaped relationship, but did not obtain a significant association between maternal blood Mn and birth outcome. This study had a small sample size (n = 101) and the maternal Mn level (16.3 μg/L) was much lower than that in our study . In ShanMany studies reported the effects of Mn deficiency in animals, but human study is rare  to our kThis study has a relatively small number of observations, especially at high Mn concentration range, which obscures the relationship at very high levels of maternal blood Mn. In addition, as we did not examine the association between umbilical cord blood Mn levels and birth weight, and maternal blood sampling during pregnancy was not measured. Thus, the temporal relationship between Mn level and birth outcome is unclear. We could not take the point that iron and Mn share uptake mechanisms into account, because the information on the maternal intake of nutritional supplement including iron and calcium, and iron-related health problems including anaemia were not available and prevalence of anaemia was very low. A study conducted in Sweden indicates that Mn level during pregnancy was not related to iron status .Our results confirm the non-linear relationship reported in a previous human study  and the Our study found that both extreme level of maternal Mn level was associated with lower birth weight outcome in a nonlinear fashion.Mn: Manganese; GAM: Generalised additive model.The authors declare that they have no competing interests.JHE analysed the data and prepared the manuscript. HKC designed the study, supervised data analysis and preparation of the manuscript. EHH designed the study and managed the MOCEH project. Supervised the birth outcome data and approved the manuscript. MH conducted and managed the data from Cheonan Center of MOCEH. Supervised the data analysis and approved the manuscript. YK conducted and managed the data from Ulsan Center of MOCEH. Supervised the data analysis and approved the manuscript. YCH conducted the quality control of the blood sample analysis, supervised the data analysis, and approved the manuscript. HSP conducted and managed the data from Seoul Center of MOCEH. Supervised the data analysis and approved the manuscript. NSC conducted and approved the nutritional data and supervised the data analysis. All authors read and approved the final manuscript.


Background and objectives: Maternal stress can depress birth weight and gestational age, with potential health effects. A growing number of studies examine the effect of maternal stress caused by environmental disasters on birth outcomes. These changes may indicate an adaptive response. In this study, we examine the effects of maternal exposure to wildfire on birth weight and gestational age, hypothesising that maternal stress will negatively influence these measures.Methodology: Using data from the Australian Capital Territory, we employed Analysis of Variance to examine the influence of the 2003 Canberra wildfires on the weight of babies born to mothers resident in fire-affected regions, while considering the role of other factors.Results: We found that male infants born in the most severely fire-affected area had significantly higher average birth weights than their less exposed peers and were also heavier than males born in the same areas in non-fire years. Higher average weights were attributable to an increase in the number of macrosomic infants. There was no significant effect on the weight of female infants or on gestational age for either sex.Conclusions and implications: Our findings indicate heightened environmental responsivity in the male cohort. We find that elevated maternal stress acted to accelerate the growth of male fetuses, potentially through an elevation of maternal blood glucose levels. Like previous studies, our work finds effects of disaster exposure and suggests that fetal growth patterns respond to maternal signals. However, the direction of the change in birth weight is opposite to that of many earlier studies. A growing body of work considers the effects of maternal exposure to stressors on fetal health, principally in terms of birth weight and gestation length, with an increased incidence of both low birth weight (birth at <2500 g) and prematurity (birth at <37 weeks gestation) being documented in populations exposed to major stressors during gestation . PretermMaternal stress is likely linked to lower weights and shorter gestations because the physiological stress response creates an energetic cost that adds to the metabolic load of gestation. An evolutionary perspective suggests that this greater load encourages reduced maternal metabolic investment in the fetus in order to aid the mother’s own chance of survival and thus her future reproductive potential . Theoretet al. [et al. [et al. [Consistent with this evolutionary theory, natural experiments demonstrate that maternal exposure to stress is associated with reduced birth weights and gestational age . For exaet al.  and Danc [et al.  find dec [et al.  find inc [et al. .et al. [Likewise, Oyarzo et al.  find an et al.  who findet al. . Similaret al. , 38.Notably, there are some exceptions to the overall trend of decreases in birth weight and gestational age. In addition to the trend of lighter and earlier neonates following the 2010 earthquake in Chile, increases in the incidence of macrosomic infants were also found and were attributed to underlying gestational diabetes mellitus (GDM) and maternal obesity . Similarin utero, as well as in early life [From an evolutionary perspective, it is also understood that stress-related differentials in maternal investment exist depending on the sex of offspring . Sex difrly life .In this study, we examine patterns in average birth weights and gestational ages following the 2003 Canberra Wildfires in the Australian Capital Territory (ACT). Wildfires expose populations to both physiological and psychosocial stressors. Some such stressors include experiences of extreme heat and poor air quality, both of which have independent effects on pregnancy , 50. PsyOn 18 January 2003, the Canberra fires burnt part of the southern and western suburbs of Canberra, Australia’s national capital, located in the ACT. The Canberra fires were the northern most tip of an 800 km fire line known collectively as the Australian Alps fires. The Canberra fires killed four people, injured 489 people, destroyed ∼500 homes and triggered the evacuation of 5000 residents. A further 50 000 residents lost essential services, representing around 15% of Canberra’s total population .Following ethics approval from The Australian National University Human Research Ethics Committee and the ACT Government Human Research Ethics Committee’s Low Risk Sub-Committee, and approval of data access by the ACT Chief Health Officer, the study used unit record data managed by the ACT Government Health Directorate Epidemiology Section  to examine birth weights and gestational ages in the ACT between 2000 and 2010.Clinical birth records in Australia are collected and administered for almost all births by hospitals and midwives . Birth rIndigenous status was recoded into a binary variable as either ‘Indigenous’  or ‘not Indigenous’. Similarly, plurality was recoded as either ‘singleton’ or ‘multiple’, with the latter category including all multiples. Lastly, divorced, separated and widowed mothers were combined in the analysis of the influence of marital status, due to small cell sizes. ‘Married’ mothers included those in common law or same-sex relationships. Maternal smoking in all analysis refers to reported smoking at any point during gestation.Three levels of fire exposure were defined using the mothers’ reported Statistical Local Area of residence at the time of birth. Mothers’ reported location of residence was used as a proxy measure of disaster exposure. The three levels of exposure we used were: ‘severely affected’, which included mothers who were resident in areas where both deaths and property damage occurred; ‘moderately affected’, which included mothers from areas where property damage (only) occurred and ‘least affected’, which was the remainder of the residential areas of Canberra, where no fire damage occurred.Because disaster impacts can be difficult to define geographically and people outside the affected zones may also experience substantial stress, the analysis included inter-year comparisons of the same areas as well as intra-year comparison between levels of disaster exposure. This allows births in each region to be compared to those in the same region in pre- and post-fire years.Analysis of variance (ANOVA) was used to examine the influence of residential location on birth weight and gestational age in the year of the fire (2003), with the three previous years (2000–02) and seven following years (2004–10), while also considering the influence of maternal age, maternal smoking during gestation, maternal Indigenous status, maternal marital status, baby’s plurality, and maternal previous pregnancy status (i.e. primigravida versus multigravida). Research indicates that multiple births, older maternal age, positive maternal Indigenous status, maternal smoking and single marital status have a depressive effect on birth weight , 54. SecBirths in 2002, 2003 and 2004 were divided into quarters to allow the effects of timing of exposure to be examined more closely, using approximate trimesters of exposure. Because previous studies indicate some sex differences in stress responsivity , 55 thisP < 0.003, df = 2), 18 g heavier in the severely affected area in 2005 , 47 g heavier in the severely affected area in 2008  and 56 g lighter in the severely affected area in 2010  when compared to those reported in the moderately affected area.ANOVAs for each year showed that average male birth weights were 197 g heavier in the severely affected area in the year of the fire (2003) , 117 g greater in the severely affected area in 2009  and 160 g greater in the severely affected area in 2010  when compared to those reported in the moderately affected area.ANOVAs for each year also showed that average female birth weights were 163 g greater in the severely affected area in 2008 . A further ANOVA which included data from all years indicates that exposed male neonates were heavier throughout 2003 than males born to mothers residing in the same areas in the previous and following years , as well as being heavier than males born elsewhere during 2003  showed that being in the severely affected area in the year of the fire was only significant for male offspring  or reported as single mothers  had babies with lighter mean birth weights [P < 0.001, df = 1) and primigravida mothers had lighter offspring than multigravida mothers  [P = 0.01).Other significant factors detected in the 2003 ANOVA on birth weight were consistent with the literature: those mothers who smoked during gestation  . Older mP = 0.02, uncorrected P = 0.01) with the largest difference occurring in individuals born between 4501 and 5000 g  and between October and December 2003 (i.e. those exposed very early in the first trimester or conceived in the fire aftermath). This positive relationship was not seen in neonates born between April and September 2003 (i.e. those exposed in the first and second trimesters). Accordingly, the relationship between birth weight and gestational length appears disrupted. While infants who were in the third or late second trimester at the time of the fire show a consistent relationship between gestational length and birth weight, the strength of this relationship declines over the remainder of 2003 (i.e. children exposed earlier in gestation or conceived in the fire aftermath) before becoming more consistent again from early 2004 onwards.P = 0.81). Similarly, there were no significant differences in the prevalence of pre-existing maternal diabetes mellitus across the three levels of fire exposure (P = 0.99).Because of the unusual pattern of higher birth weight, we explored the presence of other maternal conditions with a known relationship to birth weight disruptions including gestational diabetes and maternal smoking. Chi-square tests found no significant differences in the prevalence of GDM between the three defined areas of fire exposure in 2003 among mothers of male neonates (P < 0.001), but these declines were concentrated outside the severely affected area.Although maternal smoking was controlled for in the analysis, unreported smoking was considered as a possible relevant factor. Maternal smoking declined sharply in the ACT during the first 6 months of 2003  had a significant effect on the birth weights of exposed male fetuses, resulting in a pattern of higher birth weights with only a partially corresponding and non-significant increase in gestational length, largely in those fetuses exposed in the later stages of gestation. Because birth dates were only known by month and year, it is not possible to be more specific on the effects of exposure timing. The absence of a significant increase in gestational length suggests accelerated While we accounted for the effects of reported maternal smoking, this analysis cannot include unreported maternal smoking. During 2003, there was a decline in reported maternal smoking but this was concentrated outside the severely affected area. Assuming that unreported smoking follows similar patterns to reported smoking, changes in actual maternal smoking are unlikely to explain the increase in birth weights observed and nor would maternal smoking necessarily provide an explanation for the sex differentiation of the effect.Because macrosomia poses important health risks to both mother and neonate, potential causes of macrosomia deserve close attention. In the short term, macrosomia is associated with higher birth risks, including unplanned caesareans, assisted delivery, shoulder dystocia, newborn asphyxia and perineum tears . Over thet al. [et al. [in utero [et al. [et al. [Three studies have previously reported secondary patterns of higher birth weights or lengthened gestation following disasters: Oyarzo et al.  after a et al. , and Mar [et al.  followin [et al. . Disastein utero . Such ps [et al.  suggest  [et al.  suggest The presence of macrosomia indicates a dysregulation of maternal glucose levels. While we excluded diagnosed GDM through our analysis, it is important to note that GDM is usually screened for only once during gestation (at around 25–26 weeks) in otherwise low-risk pregnancies and has few obvious symptoms. Although high birth weights were recorded both in babies exposed to the fire before screening and in babies exposed after screening, the absence of a GDM diagnosis does not necessarily indicate the absence of any blood glucose elevation. Maternal glucose and fetal weight correlate in non-diabetic mothers, indicating that persistent increases in maternal blood glucose can increase fetal weight, even when blood glucose levels remain below those required for GDM diagnosis , 60. We Normal pregnancy triggers the action of placental steroid hormones, including corticotropin-releasing hormone  and placStress-related increases in cortisol levels would be predicted to increase circulating blood glucose via accelerated gluconeogenesis or through the disruption of glucose metabolism . As suchAlso potentially disrupting glucose metabolism are changes in food intake and physical activity. Both increased food intake and increased consumption of low-nutrition but high-calorie foods have been documented as a behavioral response to stress during pregnancy , 67. IncAlthough little is known about physical activity patterns of pregnant women during wildfires, official advice to stay indoors (due to smoke and heat) or to relocate to an evacuation centre would both have the effect of reducing normal physical activity. If reductions in physical activity occurred these would also likely alter glucose metabolism.Maternal body weight, and weight gain in pregnancy, are also good predictors of macrosomia . We wereThe Hypothalamus–Pituitary–Ovarian axis can act to upregulate steroid hormone production when nutritional energy is abundant . This inIt is well documented that male fetuses are more responsive to maternal stress than female fetuses, often measured through rates of early pregnancy loss , 68 or cIncreases in body size, particularly an increase in fetal fat reserves, could act adaptively in that they provide the infant with greater nutritional reserves when a stochastic external environment is signaled through maternal stress markers. This male responsivity indicates greater environmental sensitivity and potentially greater need for nutritional buffering due to larger average body size at birth. For example, one recent study finds that male fetal growth is accelerated under conditions of mild stress . HoweverHowever, it is equally likely that increase male macrosomia simply reflects the confluence of established male sensitivity and stress effects on maternal glucose. This response may further interact with the influence that fetal sex appears to have on maternal glucose regulation. Recent research shows that mothers of male fetuses have greater odds of developing GDM  than those carrying females. Carrying a male also further increases the effect size of usual GDM risk factors, such as older maternal age (>35 years) and non-White ethnicity .Notably, the timing of the greatest effect differs in this work from that of several previous studies. Previous studies find that prenatal stress is most impactful in early pregnancy , 5, 34, We find a pattern of fetal macrosomia associated with maternal exposure to the 2003 Canberra wildfires among male neonates, which is contrary to other similar studies in that it finds a primary pattern of macrosomia accompanied by small increases in lighter births, rather than the inverse pattern found elsewhere , 37.The study has a number of limitations. First, the definition of disaster impact assumes both a relationship to geographical area and a causal link between disaster proximity and maternal stress. Although disaster impact is not necessarily geographically limited, no stronger method of defining disaster exposure is available when working within the constraints of public datasets and this approach is commonly used in the literature. Second, we are limited in the specificity of our estimates of the timing of fetal exposure to the fire, as birth dates were only identified by month and year, limiting the specificity of that measure. Lastly, we are unable to directly test our hypothesis regarding maternal blood glucose elevation. This is an area which we hope to examine more closely in future work.Nevertheless, the findings of the study indicate a risk of macrosomia to exposed male infants. Fetal macrosomia poses immediate health risks to mother and child, as well as longer term health risks to the child. Our analysis finds that neither changes to maternal cigarette smoking nor changes to diagnosed rates of GDM in the population are good explanations for the observed pattern. However, elevations in maternal glucose can be sufficient to increase fetal weight without being sufficient to trigger a GDM diagnosis. Therefore, we propose that the maternal stress response precipitated an increase in maternal glucose levels that accelerated fetal growth in the more environmentally responsive male cohort. Disaster-related behavioral changes, such as a higher calorie diet and reduced physical activity, might have exacerbated this process.While our finding is contrary to the general trend of prematurity and lowered birth weights associated with disaster stress, this contrary finding does not necessarily imply that the underlying evolutionary features of the changes are similarly altered. Our findings accord with both theories of increased male frailty, as demonstrated through greater environmental responsivity, and that maternal stress acts as an indicator of future environmental quality. Potentially, higher birth weight is simply a consequence of maternal glucose rising in response to stress; however, it is also plausible that increased body weight is an adaptive response to expected future stress, albeit compromised by heightened immediate survival risks and downstream health risks.Although the timing of effects found here differs from previous work, we propose an underlying evolutionary explanation for the observed pattern. In late pregnancy, maternal investment is high and the risk of fetal loss low, because of the sunk costs of maternal investment thus far. Due to this high investment, mothers experiencing late pregnancy stress may opt for a ‘double or nothing’ strategy in which maternal investment increases to boost the chance of neonatal survival and consequent return on investment. While this strategy may disadvantage a small number of larger neonates by increasing their risk of macrosomia and its complications, for the majority such a strategy would provide an unproblematic increase in body weight which provides a buffer against environmental stress.Importantly, our results are consistent with previous findings in that they find an association between disaster exposure and changes in birth outcomes that threaten maternal and fetal health. Thus, the broader implementation of maternal stress management as an aspect of disaster response is lent further support by this work.