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1.  Effects of Prenatal and Perinatal Exposure to Fine Air Pollutants and Maternal Fish Consumption on the Occurrence of Infantile Eczema 
As there is a scarcity of evidence on potential hazards and preventive factors for infantile eczema operating in the prenatal period, the main goal of this study was to assess the role of prenatal exposure to fine particulate matter and environmental tobacco smoke (ETS) in the occurrence of infant eczema jointly with the possible modulating effect of maternal fish consumption.
The study sample consisted of 469 women enrolled during pregnancy, who gave birth to term babies (>36 weeks of gestation). Among all pregnant women recruited, personal measurements of fine particulate matter (PM2.5) were performed over 48 h in the second trimester of pregnancy. After delivery, every 3 months in the first year of the newborn's life, a detailed, standardized, face-to-face interview was administered to each mother, in the process of which a trained interviewer recorded any history of infantile eczema and data on potential environmental hazards. The estimated risk of eczema related to higher prenatal exposure to fine particulate matter (PM2.5 >53.0 μg/m3) and postnatal ETS as well as the protective effect of maternal fish intake were adjusted for potential confounders in a multivariable logistic regression model.
While the separate effects of higher prenatal PM2.5 and postnatal ETS exposure were not statistically significant, their joint effect appeared to have a significant influence on the occurrence of infantile eczema [odds ratio 2.39, 95% confidence interval (CI) 1.10–5.18]. With maternal fish intake of more than 205 g/week, the risk of eczema decreased by 43% (odds ratio 0.57, 95% CI 0.35–0.93). The incidence rate ratio (IRR) for eczema symptoms, estimated from the Poisson regression model, was increased with both higher exposure to prenatal PM2.5 and postnatal ETS (IRR 1.55, 95% CI 0.99–2.44) and in children of atopic mothers (IRR 1.35, 95% CI 1.04–1.75) but was lower in girls (IRR 0.78, 95% CI 0.61–1.00). The observed preventive effect of fish consumption on the frequency of eczema symptoms was consistent with the results of the logistic analysis (IRR 0.72, 95% CI 0.52–0.99).
The findings indicate that higher prenatal exposure to fine particulate matter combined with postnatal exposure to ETS may increase the risk of infant eczema, while maternal fish intake during pregnancy may reduce the risk of infantile eczema.
PMCID: PMC3047761  PMID: 21293147
Fish consumption; Prenatal exposure to fine particles; Cow's milk allergy; Passive tobacco smoke; Cohort study
2.  Gender differences in fetal growth of newborns exposed prenatally to airborne fine particulate matter 
Environmental research  2009;109(4):447-456.
Our primary purpose was to assess sex-specific fetal growth reduction in newborns exposed prenatally to fine particulate matter. Only women 18–35 years of age, who claimed to be non-smokers, with singleton pregnancies, without illicit drug use and HIV infection, free from chronic diseases were eligible for the study. A total of 481 enrolled pregnant women who gave birth between 37 and 43 weeks of gestation were included in the study. Prenatal personal exposure to fine particles over 48 h during the second trimester was measured using personal monitors. To evaluate the relationship between the level of PM2.5 measured over 48 h in the second trimester of pregnancy with those in the first and the third trimesters, a series of repeated measurements in each trimester was carried out in a random subsample of 85 pregnant women. We assessed the effect of PM2.5 exposure on the birth outcomes (weight, length and head circumference at birth) by multivariable regression models, controlling for potential confounders (maternal education, gestational age, parity, maternal height and prepregnancy weight, sex of infant, prenatal environmental tobacco smoke, and season of birth). Birth outcomes were associated positively with gestational age, parity, maternal height and prepregnancy weight, but negatively with the level of prenatal PM2.5 exposure. Overall average increase in gestational period of prenatal exposure to fine particles by about 30 μg/m3, i.e., from 25th percentile (23.4 μg/m3) to 75th percentile (53.1 μg/m3) brought about an average birth weight deficit of 97.2 g (95% CI: −201, 6.6) and length at birth of 0.7cm (95% CI: −1.36, −0.04). The corresponding exposure lead to birth weight deficit in male newborns of 189 g (95% CI: −34.2, −343) in comparison to 17 g in female newborns; the deficit of length at birth in male infants amounted to 1.1 cm (95% CI: −0.11, −2.04). We found a significant interrelationship between self-reported ETS and PM2.5, however, none of the models showed a significant interaction of both variables. The joint effect of various levels of PM2.5 and ETS on birth outcomes showed the significant deficit only for the categories of exposure with higher component of PM2.5. Concluding, the results of the study suggest that observed deficits in birth outcomes are rather attributable to prenatal PM2.5 exposure and not to environmental tobacco smoke. The study also provided evidence that male fetuses are more sensitive to prenatal PM2.5 exposure and this should persuade policy makers to consider birth outcomes by gender separately while setting air pollution guidelines.
PMCID: PMC3786262  PMID: 19261271
Cohort study; Prenatal exposure; Air pollutants; Fine particles; Gender; Fetal growth deficits
3.  Maternal Influenza Immunization and Reduced Likelihood of Prematurity and Small for Gestational Age Births: A Retrospective Cohort Study 
PLoS Medicine  2011;8(5):e1000441.
In an analysis of surveillance data from the state of Georgia (US), Saad Omer and colleagues show an association between receipt of influenza vaccination among pregnant women and reduced risk of premature births.
Infections during pregnancy have the potential to adversely impact birth outcomes. We evaluated the association between receipt of inactivated influenza vaccine during pregnancy and prematurity and small for gestational age (SGA) births.
Methods and Findings
We conducted a cohort analysis of surveillance data from the Georgia (United States) Pregnancy Risk Assessment Monitoring System. Among 4,326 live births between 1 June 2004 and 30 September 2006, maternal influenza vaccine information was available for 4,168 (96.3%). The primary intervention evaluated in this study was receipt of influenza vaccine during any trimester of pregnancy. The main outcome measures were prematurity (gestational age at birth <37 wk) and SGA (birth weight <10th percentile for gestational age). Infants who were born during the putative influenza season (1 October–31 May) and whose mothers were vaccinated against influenza during pregnancy were less likely to be premature compared to infants of unvaccinated mothers born in the same period (adjusted odds ratio [OR] = 0.60; 95% CI, 0.38–0.94). The magnitude of association between maternal influenza vaccine receipt and reduced likelihood of prematurity increased during the period of at least local influenza activity (adjusted OR = 0.44; 95% CI, 0.26–0.73) and was greatest during the widespread influenza activity period (adjusted OR = 0.28; 95% CI, 0.11–0.74). Compared with newborns of unvaccinated women, newborns of vaccinated mothers had 69% lower odds of being SGA (adjusted OR = 0.31; 95% CI, 0.13–0.75) during the period of widespread influenza activity. The adjusted and unadjusted ORs were not significant for the pre-influenza activity period.
This study demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. However, no associations were found for the pre-influenza activity period. Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of SGA birth.
Please see later in the article for the Editors' Summary
Editors' Summary
Maternal infections during pregnancy can have harmful effects on both mother and baby. For example, influenza is associated with increased morbidity and mortality among pregnant women compared to women who are not pregnant or who acquire influenza infection after delivery. And some respiratory infections, especially those that can cause maternal pneumonia such as influenza virus, are known to be associated with the baby being small—below the 10th percentile—for gestational age and with an increased risk of preterm birth—birth before 37 weeks of gestation. Previous studies have shown that inactivated influenza vaccination during pregnancy provides protection against influenza virus for both mother and baby. As there has been an increase in the rate of preterm birth the United States from 9.5% in 1981 to 12.8% in 2006, the impact of maternal influenza immunization on birth outcomes has important public health implications and is of particular interest during influenza pandemics.
Why Was This Study Done?
Given that maternal vaccination can protect babies from influenza virus, it is plausible that influenza vaccination in pregnancy could mitigate adverse birth outcomes such as prematurity and the baby being small for gestational age. The researchers of this study set out to evaluate this hypothesis by investigating whether there was an association between women receiving inactivated influenza vaccine during pregnancy and positive birth outcomes for their babies in the population of the state of Georgia, in the United States.
What Did the Researchers Do and Find?
The researchers conducted a retrospective cohort analysis of a large surveillance dataset (the Georgia Pregnancy Risk Assessment Monitoring System) to analyze the relationship between receipt of inactivated influenza vaccine during any trimester of pregnancy by mothers of infants born between June 1, 2004, and September 30, 2006, and their baby being premature or small for gestational age. The study period encompassed the 2004–2005 and 2005–2006 influenza seasons—the two most recent seasons for which the data were available. The researchers did a stratified analysis for the overall study period, and various periods during it, and also weighted their analysis to adjust for possible oversampling. They used logistic regression to evaluate the association of maternal influenza vaccine and (a) prematurity and (b) small for gestational age, and also used linear regression to evaluate the statistical significance of differences between vaccinated and unvaccinated women for mean gestational age at first antenatal visit and mean birth weight.
During the study period, 4,168 mother–baby pairs were included in the analysis. Local influenza activity was detected during 27 weeks (22.1%), and 578 women (14.9% [weighted]) had received the influenza vaccine during pregnancy, giving a vaccination coverage of 19.2% (weighted) among mothers of infants born during the assumed influenza season. In the study sample, 1,547 babies (10.6% [weighted]) were born premature, and 1,186 babies (11.2% [weighted]) were small for gestational age. Infants who were born during the assumed influenza season (October–May) and whose mothers were vaccinated against influenza during pregnancy were less likely to be premature than infants of unvaccinated mothers born in the same period, with an adjusted odds ratio of 0.60. The effect of maternal influenza vaccine on reducing prematurity was the highest for infants born during the period of widespread influenza activity, with 72% lower odds of prematurity in infants of vaccinated mothers than infants of unvaccinated mothers. Compared with newborns of unvaccinated women, babies of vaccinated mothers also had 69% lower odds of being small for gestational age during the period of widespread influenza activity, but the adjusted and unadjusted odd ratios were not significant for the pre-influenza activity period.
What Do These Findings Mean?
These results show that there was an association between maternal immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. In addition, during the period of widespread influenza activity there was an negative association between maternal receipt of influenza vaccine and small for gestational age birth.
Additional Information
Please access these Web sites via the online version of this summary at
More information about influenza vaccination during pregnancy is available from the World Health Organization and the UK National Health Service
More information about the Georgia Pregnancy Risk Assessment Monitoring System is also available
PMCID: PMC3104979  PMID: 21655318
4.  Risk of Adverse Pregnancy Outcomes among Women Practicing Poor Sanitation in Rural India: A Population-Based Prospective Cohort Study 
PLoS Medicine  2015;12(7):e1001851.
The importance of maternal sanitation behaviour during pregnancy for birth outcomes remains unclear. Poor sanitation practices can promote infection and induce stress during pregnancy and may contribute to adverse pregnancy outcomes (APOs). We aimed to assess whether poor sanitation practices were associated with increased risk of APOs such as preterm birth and low birth weight in a population-based study in rural India.
Methods and Findings
A prospective cohort of pregnant women (n = 670) in their first trimester of pregnancy was enrolled and followed until birth. Socio-demographic, clinical, and anthropometric factors, along with access to toilets and sanitation practices, were recorded at enrolment (12th week of gestation). A trained community health volunteer conducted home visits to ensure retention in the study and learn about study outcomes during the course of pregnancy. Unadjusted odds ratios (ORs) and adjusted odds ratios (AORs) and 95% confidence intervals for APOs were estimated by logistic regression models. Of the 667 women who were retained at the end of the study, 58.2% practiced open defecation and 25.7% experienced APOs, including 130 (19.4%) preterm births, 95 (14.2%) births with low birth weight, 11 (1.7%) spontaneous abortions, and six (0.9%) stillbirths. Unadjusted ORs for APOs (OR: 2.53; 95% CI: 1.72–3.71), preterm birth (OR: 2.36; 95% CI: 1.54–3.62), and low birth weight (OR: 2.00; 95% CI: 1.24–3.23) were found to be significantly associated with open defecation practices. After adjustment for potential confounders such as maternal socio-demographic and clinical factors, open defecation was still significantly associated with increased odds of APOs (AOR: 2.38; 95% CI: 1.49–3.80) and preterm birth (AOR: 2.22; 95% CI: 1.29–3.79) but not low birth weight (AOR: 1.61; 95% CI: 0.94–2.73). The association between APOs and open defecation was independent of poverty and caste. Even though we accounted for several key confounding factors in our estimates, the possibility of residual confounding should not be ruled out. We did not identify specific exposure pathways that led to the outcomes.
This study provides the first evidence, to our knowledge, that poor sanitation is associated with a higher risk of APOs. Additional studies are required to elucidate the socio-behavioural and/or biological basis of this association so that appropriate targeted interventions might be designed to support improved birth outcomes in vulnerable populations. While it is intuitive to expect that caste and poverty are associated with poor sanitation practice driving APOs, and we cannot rule out additional confounders, our results demonstrate that the association of poor sanitation practices (open defecation) with these outcomes is independent of poverty. Our results support the need to assess the mechanisms, both biological and behavioural, by which limited access to improved sanitation leads to APOs.
Pinaki Panigrahi and colleagues examine the association between adverse pregnancy outcomes and sanitation practices in pregnant women in rural India.
Editors' Summary
Pregnancy is usually a happy time for women and their families. But, for some women, pregnancy ends unhappily. Some women lose their baby during early pregnancy (spontaneous abortion or miscarriage) or during late pregnancy (stillbirth). Others have their baby earlier than expected (preterm birth) or have a baby with low birth weight, two outcomes that adversely affect the baby’s survival and long-term health. The burden of adverse pregnancy outcomes (low birth weight, preterm birth, stillbirth, and spontaneous abortion) is substantial across the world but is particularly high in resource-limited settings. More than 60% of all preterm births take place in Asia and sub-Saharan Africa, and in India alone nearly 13 million babies (47% of all births) had a low birth weight in 2010. Many risk factors for adverse pregnancy outcomes have been identified, including infection, diabetes, poor antenatal care, and other socio-economic factors, but a clear causal mechanism for adverse pregnancy outcomes has not been established.
Why Was This Study Done?
One potential risk factor for adverse pregnancy outcomes, particularly in resource-limited settings, is poor sanitation—the inadequate provision of facilities and services for the safe disposal of human urine and feces. The WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation estimates that, globally, 1.1 billion people defecate in the open, a practice that can expose individuals to contact with human feces containing infectious organisms and that can contaminate food and water. Poor sanitation might contribute to adverse pregnancy outcomes by promoting infection or by causing stress during pregnancy. Women might, for example, limit their intake of food and water to avoid having to use inadequate toilet facilities, thereby adversely affecting the health of their unborn child. Here, the researchers assess whether poor sanitation practices are associated with an increased risk of adverse pregnancy outcomes by undertaking a population-based prospective study in two rural areas of Odisha state, India. Odisha has a high infant death rate (57 deaths per 1,000 live births), only 18.2% of households have access to an improved latrine (a facility such as a flush toilet that hygienically prevents human contact with human excreta), and 75% of households practice open defecation.
What Did the Researchers Do and Find?
For their study, the researchers enrolled 670 women during the first trimester of their pregnancy. They recorded socio-demographic data (for example, age, level of education, and household assets), clinical data, weight and height, and toilet access and sanitation practices for each woman at enrollment and followed them through pregnancy until birth. Nearly two-thirds of the women practiced open defecation, and a quarter experienced an adverse pregnancy outcome, most commonly a preterm birth and/or having a baby with low birth weight. After adjustment for potential confounding factors (factors that might affect outcomes, such as socio-demographic characteristics), open defecation was significantly associated with adverse pregnancy outcomes (all four adverse outcomes considered together) and with preterm birth, but not with low birth weight (a significant association is one that is unlikely to have happened by chance). Specifically, the adjusted odds ratios (an indicator of the strength of association between an exposure and an outcome; an odds ratio of more than one indicates that an exposure increases the risk of an outcome) of adverse pregnancy outcomes and preterm birth among women practicing open defecation compared with women with access to a latrine were 2.38 and 2.22, respectively. Notably, these associations were independent of poverty, caste, and religion.
What Do These Findings Mean?
These findings indicate that, among women in Odisha, defecation in the open (poor sanitation) during pregnancy is associated with a higher risk of any adverse pregnancy outcome and of preterm birth than the use of a latrine. Counterintuitively, these findings also suggest that the association between open defecation and adverse pregnancy outcomes is not explained by poverty. Although the researchers adjusted for numerous confounding factors in their analysis, the women who defecated in the open may have shared some other unknown characteristic (residual confounding) that was actually responsible for their increased risk of an adverse pregnancy outcome. Further studies are now needed to determine the socio-behavioral and/or biological basis of the association between poor sanitation and adverse pregnancy outcomes. Appropriate public health interventions can then be designed to reduce the burden of adverse pregnancy outcomes among women living in settings where there is limited access to adequate sanitation.
Additional Information
This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at
The March of Dimes, a non-profit organization for pregnancy and baby health, provides information on pregnancy loss, preterm birth, and low birth weight
Tommy’s, a UK non-profit organization that funds research into stillbirth, premature birth, and miscarriage, also provides information about adverse pregnancy outcomes
The World Health Organization (WHO) provides information on water, sanitation, and health (in several languages)
The WHO/UNICEF Joint Monitoring Programme for Water Supply and Sanitation monitors progress toward improved global sanitation; its 2014 report on progress in water sanitation is available (in several languages)
The children’s charity UNICEF, which protects the rights of children and young people around the world, provides information on water, sanitation, and health (in several languages)
The Water Supply and Sanitation Collaborative Council and the non-governmental organization Practical Action provide information on approaches and technologies for improving sanitation
A PLOS Medicine Collection on water and sanitation and a Policy Forum by Velleman et al. on improving water, sanitation, and hygiene for maternal and newborn health are available
PMCID: PMC4511257  PMID: 26151447
5.  Estimated Risk for Altered Fetal Growth Resulting from Exposure to Fine Particles during Pregnancy: An Epidemiologic Prospective Cohort Study in Poland 
Environmental Health Perspectives  2004;112(14):1398-1402.
The purpose of this study was to estimate exposure of pregnant women in Poland to fine particulate matter [≤2.5 μm in diameter (PM2.5)] and to assess its effect on the birth outcomes. The cohort consisted of 362 pregnant women who gave birth between 34 and 43 weeks of gestation. The enrollment included only nonsmoking women with singleton pregnancies, 18–35 years of age, who were free from chronic diseases such as diabetes and hypertension. PM2.5 was measured by personal air monitoring over 48 hr during the second trimester of pregnancy. All assessed birth effects were adjusted in multiple linear regression models for potential confounding factors such as the size of mother (maternal height, prepregnancy weight), parity, sex of child, gestational age, season of birth, and self-reported environmental tobacco smoke (ETS). The regression model explained 35% of the variability in birth weight (β = −200.8, p = 0.03), and both regression coefficients for PM2.5 and birth length (β = −1.44, p = 0.01) and head circumference (HC; β = −0.73, p = 0.02) were significant as well. In all regression models, the effect of ETS was insignificant. Predicted reduction in birth weight at an increase of exposure from 10 to 50 μg/m3 was 140.3 g. The corresponding predicted reduction of birth length would be 1.0 cm, and of HC, 0.5 cm. The study provides new and convincing epidemiologic evidence that high personal exposure to fine particles is associated with adverse effects on the developing fetus. These results indicate the need to reduce ambient fine particulate concentrations. However, further research should establish possible biologic mechanisms explaining the observed relationship.
PMCID: PMC1247567  PMID: 15471732
air pollutants; cohort study; fetal growth; pregnancy; prenatal exposure
We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes.
The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years of age, and who were free from chronic diseases such as diabetes and hypertension were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS).
The multivariable regression model showed a significant deficit in birthweight associated with barbecued meat consumption in pregnancy (coeff = −106.0 g; 95%CI: −293.3, −35.8); The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = −164.6 g; 95%CI: −172.3, − 34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: −419.0, − 9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birthweight could not have been mediated by shortened gestation period.
In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.
PMCID: PMC3288524  PMID: 22079395
barbecued meat; pregnancy; birth weight; birth cohort study
7.  Prenatal exposure to polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) may influence birth weight among infants in a Swedish cohort with background exposure: a cross-sectional study 
Environmental Health  2013;12:44.
Prenatal exposure to persistent organic pollutants, e.g. polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) has been suggested to negatively affect birth weight although epidemiological evidence is still inconclusive. We investigated if prenatal exposure to PCBs and PBDEs is related to birth weight in a Swedish population with background exposure.
Breast milk was sampled during the third week after delivery from first-time mothers in Uppsala county, Sweden 1996–2010 (POPUP cohort) (N = 413). Samples were analysed for di-ortho PCBs (CB-138, 153, 180) and tetra- to hexa- brominated PBDEs (BDE-47, 99, 100, 153). Simple and multiple linear regression models were used to investigate associations between lipid-adjusted, ln-transformed PCB and PBDE concentrations, and birth weight. Covariates included in the multivariate regression model were PCB and PBDE exposure, maternal age, pre-pregnancy BMI, weight gain during pregnancy, education, smoking, gender of the infant and gestational length. The effect of including fish consumption was also investigated.
In the multivariate model, prenatal exposure to di-ortho PCBs was significantly associated with increased birth weight (β = 137; p = 0.02). The result did not change when gestational length was added to the model. An inverse association between PBDE(4) (sum of BDE-47, -99, -100 and −153) and birth weight was observed in the multivariate model including gestational length (β = −106; p = 0.04). Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders of the association between di-ortho PCBs and birth weight. The associations were not alleviated after adjustment for fish consumption, a major source of PCB and PBDE exposure. The observed associations were stronger for boys than for girls.
Our results indicate that prenatal exposure to di-ortho PCBs and PBDE(4) may influence birth weight in different directions, i.e. PCB exposure was associated with higher birth weight and PBDE exposure with lower birth weight. Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders that may hide positive association between di-ortho PCB exposure and birth weight if they are not included in the statistical model. We speculate that even small PCB- and PBDE-induced shifts in the distribution of birth weight may influence future public health in populations with background exposure.
PMCID: PMC3673870  PMID: 23724965
Birth weight; Breast milk; PBDE; PCB; BMI; Weight gain; Fish consumption
8.  Maternal Fish Consumption and Infant Birth Size and Gestation: New York State Angler Cohort Study 
The scientific literature poses a perplexing dilemma for pregnant women with respect to the consumption of fish from natural bodies of water. On one hand, fish is a good source of protein, low in fat and a rich source of other nutrients all of which have presumably beneficial effects on developing embryos and fetuses. On the other hand, consumption of fish contaminated with environmental toxicants such as polychlorinated biphenyls (PCBs) has been associated with decrements in gestation and birth size.
2,716 infants born between 1986–1991 to participants of the New York State Angler Cohort Study were studied with respect to duration of maternal consumption of contaminated fish from Lake Ontario and its tributaries and gestation and birth size. Hospital delivery records (maternal and newborn) were obtained for 92% of infants for the ascertainment of gestation (weeks), birth size (weight, length, chest, and head circumference) and other known determinants of fetal growth (i.e., maternal parity, history of placental infarction, uterine bleeding, pregnancy loss or cigarette smoking and infant's race, sex and presence of birth defect). Duration of maternal fish consumption prior to the index infant's birth was categorized as: none; 1–2, 3–7, 8+ years, while birth weight (in grams), birth length (in centimeters), and head and chest circumference (in centimeters) were left as continuous variables in multiple linear regression models. Birth size percentiles, ponderal indices and head to chest circumference ratios were computed to further assess proportionality and birth size in relation to gestational age.
Analysis of variance failed to identify significant mean differences in gestation or any measure of birth size in relation to duration of maternal lifetime fish consumption. Multiple linear regressions identified gestational age, male sex, number of daily cigarettes, parity and placental infarction, as significant determinants of birth size.
The results support the absence of an adverse relation between Lake Ontario fish consumption and reduced birth size as measured by weight, length and head circumference. Biological determinants and maternal cigarette smoking during pregnancy remain important determinants of birth size.
PMCID: PMC165589  PMID: 12826023
9.  Using new satellite based exposure methods to study the association between pregnancy pm2.5 exposure, premature birth and birth weight in Massachusetts 
Environmental Health  2012;11:40.
Adverse birth outcomes such as low birth weight and premature birth have been previously linked with exposure to ambient air pollution. Most studies relied on a limited number of monitors in the region of interest, which can introduce exposure error or restrict the analysis to persons living near a monitor, which reduces sample size and generalizability and may create selection bias.
We evaluated the relationship between premature birth and birth weight with exposure to ambient particulate matter (PM2.5) levels during pregnancy in Massachusetts for a 9-year period (2000–2008). Building on a novel method we developed for predicting daily PM2.5 at the spatial resolution of a 10x10km grid across New-England, we estimated the average exposure during 30 and 90 days prior to birth as well as the full pregnancy period for each mother. We used linear and logistic mixed models to estimate the association between PM2.5 exposure and birth weight (among full term births) and PM2.5 exposure and preterm birth adjusting for infant sex, maternal age, maternal race, mean income, maternal education level, prenatal care, gestational age, maternal smoking, percent of open space near mothers residence, average traffic density and mothers health.
Birth weight was negatively associated with PM2.5 across all tested periods. For example, a 10 μg/m3 increase of PM2.5 exposure during the entire pregnancy was significantly associated with a decrease of 13.80 g [95% confidence interval (CI) = −21.10, -6.05] in birth weight after controlling for other factors, including traffic exposure. The odds ratio for a premature birth was 1.06 (95% confidence interval (CI) = 1.01–1.13) for each 10 μg/m3 increase of PM2.5 exposure during the entire pregnancy period.
The presented study suggests that exposure to PM2.5 during the last month of pregnancy contributes to risks for lower birth weight and preterm birth in infants.
PMCID: PMC3464884  PMID: 22709681
Air pollution; Birth weight; Preterm birth; Aerosol optical depth; Epidemiology; PM2.5
10.  Maternal fish intake in late pregnancy and the frequency of low birth weight and intrauterine growth retardation in a cohort of British infants 
Objective: To investigate the relation between maternal fish intake in late pregnancy and the frequency of low birth weight and intrauterine growth retardation (IUGR).
Participants: 11 585 pregnant women in south west England.
Methods: Information on fish intake was obtained from a food frequency questionnaire sent to the women at 32 weeks' gestation, and used to calculate n-3 fatty acid (n-3FA) intake from fish. IUGR was defined as a birth weight for gestational age and sex below the 10th centile. Confounding variables considered included maternal age, height, weight, education, parity, smoking and drinking in pregnancy, and whether the mother was living with a partner. Only singleton, liveborn infants were included.
Main results: Mean daily intakes of fish and n-3FAs were 32.8 g and 0.147 g respectively. In unadjusted analyses there were positive associations between mean birth weight and fish intake or n-3FA intake, but these disappeared on adjustment for potential confounders. The frequency of IUGR decreased with increasing fish intake—the OR (95%CI) of IUGR in those eating no fish was 1.85 (1.44 to 2.38) compared with those in the highest fish intake group. On adjustment this relation was attenuated (adjusted OR 1.37 (1.02 to 1.84)), but the decline in the frequency of IUGR with increasing fish intake remained statistically significant. No relation was observed between mean gestation and fish or n-3FA intake.
Conclusions: These results lend some support to the hypothesis that raising fish or n3-FA intake during pregnancy may increase fetal growth rate. However, they provide no evidence that increasing fish consumption is associated with an increase in mean gestation.
PMCID: PMC1732783  PMID: 15143117
11.  Active and passive maternal smoking during pregnancy and birth outcomes: the Kyushu Okinawa Maternal and Child Health Study 
In Western countries, active maternal smoking during pregnancy is recognized as the most important preventable risk factor for adverse birth outcomes. However, the effect of passive maternal smoking is less clear and has not been extensively studied. In Japan, there has been only one epidemiological study which examined the effects of active smoking during early pregnancy on birth outcomes although the effects of passive smoking were not assessed.
Study subjects were 1565 mothers with singleton pregnancies and the babies born from these pregnancies. Data on active maternal smoking status in the first, second, and third trimesters and maternal environmental tobacco smoke (ETS) exposure at home and work were collected with self-administered questionnaires.
Compared with children born to mothers who had never smoked during pregnancy, children born to mothers who had smoked throughout their pregnancy had a significantly increased risk of small-for-gestational-age (SGA) (adjusted odd ratio [OR] = 2.87; 95% confidence interval: 1.11 − 6.56). However, active maternal smoking only in the first trimester and active maternal smoking in the second and/or third trimesters but not throughout pregnancy were not significantly associated with SGA. With regard to the risk of preterm birth, the adjusted ORs for the above-mentioned three categories were not significant; however, the positive linear trend was significant (P for trend = 0.048). No significant association was found between active maternal smoking during pregnancy and the risk of low birth weight. There was a significant inverse relationship between active maternal smoking during pregnancy and birth weight; newborns of mothers who had smoked throughout pregnancy had an adjusted mean birth weight reduction of 169.6 g. When classifying babies by gender, a significant positive association between active maternal smoking throughout pregnancy and the risk of SGA was found only in male newborns, however, the interaction was not significant. Maternal ETS exposure at home or work was not significantly associated with any birth outcomes.
This is the first study in Japan to show that active maternal smoking throughout pregnancy, but not during the first trimester, is significantly associated with an increased risk of SGA and a decrease in birth weight. Thus, women who smoke should quit smoking as soon as possible after conception.
PMCID: PMC3750375  PMID: 23919433
12.  The effect of ambient carbon monoxide on low birth weight among children born in southern California between 1989 and 1993. 
We evaluated the effect of carbon monoxide (CO) exposures during the last trimester of pregnancy on the frequency of low birth weight among neonates born 1989-1993 to women living in the Los Angeles, California, area. Using birth certificate data for that period, we assembled a retrospective cohort of infants whose mothers resided within 2 miles of 1 of 18 CO monitoring stations. Based on the gestational age and birth date of each child, we estimated last-trimester exposure by averaging the corresponding 3 months of daily CO concentrations registered at the monitoring station closest to the mother's residence (determined from the birth certificate). Where data were available (at 6 stations), we also averaged measurements taken daily for nitrogen dioxide and ozone and those taken at 6-day intervals for particulate matter [less than/equal to]10 microm (PM10) to approximate last-trimester exposures to other pollutants. Overall, the study cohort consisted of 125,573 singleton children, excluding infants born before 37 or after 44 weeks of gestation, those weighing below 1,000 or above 5,500 g at birth, those for whom fewer than 10 days of CO measurements were available during the last trimester, and those whose mothers suffered from hypertension, diabetes, or uterine bleeding during pregnancy. Within the cohort, 2,813 (2.2%) were low in birth weight (between 1,000 and 2,499 g). Exposure to higher levels of ambient CO (>5.5 ppm 3-month average) during the last trimester was associated with a significantly increased risk for low birth weight [odds ratio (OR) = 1.22; 95% confidence interval (CI), 1.03-1.44] after adjustment for potential confounders, including commuting habits in the monitoring area, sex of the child, level of prenatal care, and age, ethnicity, and education of the mother.
PMCID: PMC1566307  PMID: 9872713
13.  Low birth weight at term and the presence of fine particulate matter and carbon monoxide in the Brazilian Amazon: a population-based retrospective cohort study 
Although studies have shown an association between air pollutants from anthropogenic sources and pregnancy outcomes, little is known regarding the association between low birth weight (LBW) and exposure to emissions of biomass burning.
This population-based retrospective cohort study assessed the effect of exposure to particulate matter and carbon monoxide (CO) from biomass burning in the Amazon and cerrado (Brazilian savanna) biomes on term LBW (<2500 g) in cities of Mato Grosso, Brazil. Data on births were obtained from the Information System on Live Births of the Ministry of Health. The exclusion criteria were a twin pregnancy, gestational age of less than 37 weeks, and congenital malformation diagnosed at birth. For exposure variables, we used a historical series of daily average concentrations of particulate matter with a diameter less than 2.5 μm (PM2.5) and CO provided by Coupled Aerosol and Trace Gases Transport Model for the Brazilian Development of the Regional Atmospheric Modeling System developed at the National Institute for Space National Center for Weather Forecasts and Climate Studies, National Institute for Space Research. Maternal exposure was estimated by the average amount of pollutants for each trimester and for the entire period of gestation. The association between air pollutants and LBW was analyzed by multiple logistic regression, adjusting for the newborn’s sex, mother’s age and education, and prenatal care.
A total of 6147 full-term singleton live births were included in the study and 193 (3.1%) were LBW. In adjusted analysis, the number of prenatal visits and maternal education with 8 years or more were associated with LBW. The association between exposure to air pollutants and the risk of LBW was significant for the 4th quartile of PM2.5 concentrations in the 2nd trimester (OR = 1.51, 95% CI = 1.04 to 2.17) and in the 3rd trimester, and for the 4th quartile of CO concentrations in the 2nd trimester only, in adjusted analysis.
This study provides further evidence of the effect of smoke from biomass burning on the occurrence of LBW in cities of the Brazilian Amazon.
PMCID: PMC4162928  PMID: 25193316
Newborn; Low birth weight; Air pollutants; Population-based; Case–control; Brazilian Amazon
14.  Relationship of the intake of different food groups by pregnant mothers with the birth weight and gestational age: Need for public and individual educational programs 
This study was conducted to investigate the relationship between the intake of different food groups by pregnant mothers and neonatal low birth weight and premature births.
Materials and Methods:
In this cohort, the target population was 225 pregnant women, randomly selected from different geographical areas of the city of Isfahan, Iran (from April to September, 2012). The main variables in the study were weight and gestational age of the neonates and the type and amount of different food groups used by the mothers. All nutritional variables were compared according to different groups of infants (normal, premature, and low birth weight). In the multivariate analysis, multiple linear and logistic regression models were used to identify those different food frequency questionnaire (FFQ) variables independently associated with the newborn's weight and gestational age, adjusted by maternal consumption of calcium supplementation, folic acid, and omega-3, during pregnancy.
A total of 214 (47.7% boys) infants with complete information were included. They had a mean gestational age of 38.72 ± 1.2 weeks. The mean birth weight was 3.11 ± 0.384 kg. The percentages of premature and low birth weight (LBW) infants were 7 and 5%, respectively. At multiple logistic regression controlling for potentially confounding factors that were significantly associated with prematurity and LBW at univariate analysis (maternal consumption of calcium supplementation, folic acid, and omega-3, during pregnancy), type of nutritional groups containing dairy products, proteins, fish, and shrimp group, as well as fruits and vegetables, had a significant positive association with increasing the gestational age (P < 0.05). The group that consumed proteins, fish, and shrimp, as well as fruits and vegetables had a significant positive association with the newborn's weight (P < 0.05).
This study indicated the importance of proper nutrition on reducing the rates of LBW and premature births. Comprehensive educational programs at individual and public levels are warranted in this regard.
PMCID: PMC4392531  PMID: 25883993
Education; fetal growth; health promotion; maternal nutrition; pregnancy
15.  Ambient air pollution exposure and full-term birth weight in California 
Environmental Health  2010;9:44.
Studies have identified relationships between air pollution and birth weight, but have been inconsistent in identifying individual pollutants inversely associated with birth weight or elucidating susceptibility of the fetus by trimester of exposure. We examined effects of prenatal ambient pollution exposure on average birth weight and risk of low birth weight in full-term births.
We estimated average ambient air pollutant concentrations throughout pregnancy in the neighborhoods of women who delivered term singleton live births between 1996 and 2006 in California. We adjusted effect estimates of air pollutants on birth weight for infant characteristics, maternal characteristics, neighborhood socioeconomic factors, and year and season of birth.
3,545,177 singleton births had monitoring for at least one air pollutant within a 10 km radius of the tract or ZIP Code of the mother's residence. In multivariate models, pollutants were associated with decreased birth weight; -5.4 grams (95% confidence interval -6.8 g, -4.1 g) per ppm carbon monoxide, -9.0 g (-9.6 g, -8.4 g) per pphm nitrogen dioxide, -5.7 g (-6.6 g, -4.9 g) per pphm ozone, -7.7 g (-7.9 g, -6.6 g) per 10 μg/m3 particulate matter under 10 μm, -12.8 g (-14.3 g, -11.3 g) per 10 μg/m3 particulate matter under 2.5 μm, and -9.3 g (-10.7 g, -7.9 g) per 10 μg/m3 of coarse particulate matter. With the exception of carbon monoxide, estimates were largely unchanged after controlling for co-pollutants. Effect estimates for the third trimester largely reflect the results seen from full pregnancy exposure estimates; greater variation in results is seen in effect estimates specific to the first and second trimesters.
This study indicates that maternal exposure to ambient air pollution results in modestly lower infant birth weight. A small decline in birth weight is unlikely to have clinical relevance for individual infants, and there is debate about whether a small shift in the population distribution of birth weight has broader health implications. However, the ubiquity of air pollution exposures, the responsiveness of pollutant levels to regulation, and the fact that the highest pollution levels in California are lower than those regularly experienced in other countries suggest that precautionary efforts to reduce pollutants may be beneficial for infant health from a population perspective.
PMCID: PMC2919523  PMID: 20667084
16.  Cryptorchidism and Maternal Alcohol Consumption during Pregnancy 
Environmental Health Perspectives  2006;115(2):272-277.
Prenatal exposure to alcohol can adversely affect the fetus. We investigated the association between maternal alcohol consumption during pregnancy and cryptorchidism (undescended testis) among newborn boys.
We examined 2,496 boys in a prospective Danish–Finnish birth cohort study for cryptorchidism at birth (cryptorchid/healthy: 128/2,368) and at 3 months of age (33/2,215). Quantitative information on alcohol consumption (average weekly consumption of wine, beer, and spirits and number of binge episodes), smoking, and caffeine intake was obtained by questionnaire and/or interview once during the third trimester of pregnancy, before the outcome of the pregnancy was known. For a subgroup (n = 465), information on alcohol consumption was obtained twice during pregnancy by interviews.
We investigated maternal alcohol consumption both as a continuous variable and categorized. The odds for cryptorchidism increased with increasing weekly alcohol consumption. After adjustment for confounders (country, smoking, caffeine intake, binge episodes, social class, maternal age, parity, maturity, and birth weight) the odds remained significant for women with a weekly consumption of five or more alcoholic drinks (odds ratio = 3.10; 95% confidence interval, 1.05–9.10).
Regular alcohol intake during pregnancy appears to increase the risk of congenital cryptorchidism in boys. The mechanisms for this association are unknown. Counseling of pregnant women with regard to alcohol consumption should also consider this new finding.
PMCID: PMC1817679  PMID: 17384777
alcohol; caffeine; cohort studies; cryptorchidism; risk factors; smoking
17.  Sources of greater fetal vulnerability to airborne polycyclic aromatic hydrocarbons among African Americans 
This study attempted to clarify the household and mother’s lifestyle factors that contribute to the greater fetal vulnerability of African-American individuals to airborne polycyclic aromatic hydrocarbons (PAH).
Non-smoking pregnant women with no known risks of adverse birth outcome were monitored for their personal exposure to airborne PAH. Birth outcomes were collected from the hospital medical record. Modification of the airborne PAH effects was statistically examined. In linear regression analyses, modification of PAH effect by demographic, socioeconomic and behavioural traits on birth weight and fetal growth ratio were respectively tested, adjusting for the gestational age, gender, parity, delivery season, maternal body mass index and weight gained during the present pregnancy.
Maternal obesity exacerbated the airborne PAH risk by −491 g per 25th to 80th percentile unit exposure (95% CI −197 to −786 g; p<0.01) among African Americans. In addition, frequent dietary intake of smoked, grilled or barbequed items independently reduced the birth weight of African-American newborns by −204 g (95% CI −21 to −387 g; p=0.03).
Maternal obesity significantly exacerbated the risk of prenatal PAH exposure in African-American newborns. Also, frequent dietary consumption of PAH-laden food items posed an independent risk on the reduced birth weight among African Americans.
PMCID: PMC3201730  PMID: 20805195
18.  Vitamin D supplementation in pregnancy: A systematic review 
It is unclear whether the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25(OH)-vitamin D during pregnancy, and how this might best be achieved. CRD42011001426.
Aim/ Research Questions
What are the clinical criteria for vitamin D deficiency in pregnant women?What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)-vitamin D?Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)?What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy?Is supplementation with vitamin D in pregnancy likely to be cost-effective?
We performed systematic review and where possible combined study results using meta-analysis to estimate the combined effect size.
Major electronic databases were searched up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary.
Inclusion and exclusion criteria
Pregnant women or pregnant women and their offspring.
Either assessment of vitamin D status (dietary intake, sunlight exposure, circulating 25(OH)-vitamin D concentration) or supplementation of participants with vitamin D or vitamin D containing food e.g. oily fish.
Offspring: Birth weight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes, low birth weight, serum calcium concentration, blood pressure and rickets. Mother: Preeclampsia, gestational diabetes, risk of caesarean section and bacterial vaginosis.
76 studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence.
The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes.
For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)-vitamin D and 1) offspring birth weight in meta-analysis of 3 observational studies using log-transformed 25(OH)-vitamin D concentrations after adjustment for potential confounding factors (pooled regression coefficient 5.63g/10% change maternal 25(OH)D, 95% CI 1.11,10.16), but not in those 4 studies using natural units, or across intervention studies; 2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of 6 intervention studies (all found to be at high risk of bias; mean difference 0.05mmol/l, 95% CI 0.02, 0.05); and 3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis.
The evidence base was insufficient to reliably answer questions 4 and 5.
Study methodology varied widely in terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition.
The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)-vitamin D status and offspring birth weight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birth weight, bone mass) or risk of bias and low quality (calcium concentrations). High quality randomised trials are now required.
PMCID: PMC4124722  PMID: 25025896
19.  The effect of maternal prenatal smoking and alcohol consumption on the placenta-to-birth weight ratio 
Placenta  2014;35(7):437-441.
Maternal influence on fetal growth is mediated through the placenta and this influence may have an implication for the offspring’s long-term health. The placenta-to-birth weight ratio has been regarded as an indicator of placental function. However, few studies have examined the effect of maternal lifestyle exposures on the placenta-to-birth weight ratio. This study aims to examine the associations of maternal prenatal smoking and alcohol consumption with the placenta-to-birth weight ratio.
Data for 7945 term singletons, gestation ≥37 weeks, were selected from the Tasmanian Infant Health Survey; a 1988–1995 Australian cohort study. Placenta and birth weight were extracted from birth notification records.
Maternal smoking during pregnancy was strongly associated with a 6.77g/kg higher (95% CI 4.83 to 8.71) placenta-to-birth weight ratio when compared to non-smoking mothers. Maternal prenatal smoking was associated with lower placental (β=−15.37g; 95% CI –23.43 to -7.31) and birth weights (β=−205.49g; 95% CI −232.91 to −178.08). Mothers who consumed alcohol during pregnancy had a lower placenta–to-birth weight ratio (β=−2.07g/kg; 95% CI −4.01 to −0.12) than mothers who did not consume alcohol. The associations of maternal alcohol consumption during pregnancy with placental and birth weight did not reach statistical significance.
Maternal prenatal smoking and alcohol consumption may influence fetal growth by either directly or indirectly altering the function of the placenta.
The alteration of the in utero environment induced by smoking and alcohol consumption appears to affect placental and fetal growth in differing ways. Further studies are needed to elucidate the mechanism.
PMCID: PMC4096564  PMID: 24816479
Placenta; birthweight; pregnancy; maternal smoking; alcohol
20.  The Effect of Changing Patterns of Obstetric Care in Scotland (1980–2004) on Rates of Preterm Birth and Its Neonatal Consequences: Perinatal Database Study 
PLoS Medicine  2009;6(9):e1000153.
Jane Norman and colleagues analyzed linked perinatal surveillance data in Scotland and find that between 1980 and 2004 increases in spontaneous and medically induced preterm births contributed equally to the rising rate of preterm births.
Rates of preterm birth are rising worldwide. Studies from the United States and Latin America suggest that much of this rise relates to increased rates of medically indicated preterm birth. In contrast, European and Australian data suggest that increases in spontaneous preterm labour also play a role. We aimed, in a population-based database of 5 million people, to determine the temporal trends and obstetric antecedents of singleton preterm birth and its associated neonatal mortality and morbidity for the period 1980–2004.
Methods and Findings
There were 1.49 million births in Scotland over the study period, of which 5.8% were preterm. We found a percentage increase in crude rates of both spontaneous preterm birth per 1,000 singleton births (10.7%, p<0.01) and medically indicated preterm births (41.2%, p<0.01), which persisted when adjusted for maternal age at delivery. The greater proportion of spontaneous preterm births meant that the absolute increase in rates of preterm birth in each category were similar. Of specific maternal complications, essential and pregnancy-induced hypertension, pre-eclampsia, and placenta praevia played a decreasing role in preterm birth over the study period, with gestational and pre-existing diabetes playing an increasing role. There was a decline in stillbirth, neonatal, and extended perinatal mortality associated with preterm birth at all gestation over the study period but an increase in the rate of prolonged hospital stay for the neonate. Neonatal mortality improved in all subgroups, regardless of obstetric antecedent of preterm birth or gestational age. In the 28 wk and greater gestational groups we found a reduction in stillbirths and extended perinatal mortality for medically induced but not spontaneous preterm births (in the absence of maternal complications) although at the expense of a longer stay in neonatal intensive care. This improvement in stillbirth and neonatal mortality supports the decision making behind the 34% increase in elective/induced preterm birth in these women. Although improvements in neonatal outcomes overall are welcome, preterm birth still accounts for over 66% of singleton stillbirths, 65% of singleton neonatal deaths, and 67% of infants whose stay in the neonatal unit is “prolonged,” suggesting this condition remains a significant contributor to perinatal mortality and morbidity.
In our population, increases in spontaneous and medically induced preterm births have made equal contributions to the rising rate of preterm birth. Despite improvements in related perinatal mortality, preterm birth remains a major obstetric and neonatal problem, and its frequency is increasing.
Please see later in the article for the Editors' Summary
Editors' Summary
Most pregnancies last about 40 weeks but increasing numbers of babies are being born preterm, before they reach 37 weeks of gestation (gestation is the period during which a baby develops in its mother). Nowadays in the US, for example, more than half a million babies arrive earlier than expected every year (1 in 8 babies). Although improvements in the care of newborn babies (neonatal care) mean that preterm babies are more likely to survive than in the past, preterm birth remains the single biggest cause of infant death in many developed countries, and many preterm babies who survive have long-term health problems and disabilities, particularly those born before 32 weeks of gestation. Preterm births can be spontaneous or medically induced. At present, it impossible to predict which mothers will spontaneously deliver early and there is no effective way to prevent these preterm births; medically induced early labor is undertaken when either the unborn baby or mother would be at risk if the pregnancy continued to full term.
Why Was This Study Done?
Preterm birth rates need to be reduced, but before this can be done it is important to know how the causes of preterm birth, the numbers of preterm stillbirths, and the numbers of preterm babies who die at birth (neonatal deaths) or soon after (perinatal deaths) are changing with time. If, for example, the rise in preterm births is mainly due to an increase in medically induced labor and if this change in practice has reduced neonatal deaths, it would be unwise to try to reduce the preterm birth rate by discouraging medically induced preterm births. So far, data from the US and Latin America suggest that the increase in preterm births in these countries is solely due to increased rates of medically induced preterm births. However, in Europe and Australia, the rate of spontaneous preterm births also seems to be increasing. In this study, the researchers examine the trends over time and causes of preterm birth and of neonatal death and illness in Scotland over a 25-year period.
What Did the Researchers Do and Find?
By searching a Scottish database of linked maternity records and infant health and death records, the researchers identified 1.49 million singleton births that occurred between 1980 and 2004 of which nearly 90,000 were preterm births. Over the study period, the rates of spontaneous and of medically induced preterm births per 1,000 births increased by 10.7% and 41.2%, respectively, but because there were more spontaneous preterm births than medically induced preterm births, the absolute increase in the rates of each type of birth was similar. Several maternal complications including preeclampsia (a condition that causes high blood pressure) and placenta previa (covering of the opening of the cervix by the placenta) played a decreasing role in preterm births over the study period, whereas gestational and preexisting diabetes played an increasing role. Finally, there was a decline in stillbirths and in neonatal and perinatal deaths among preterm babies, although more babies remained in the hospital longer than 7 days after birth. More specifically, after 28 weeks of gestation, stillbirths and perinatal deaths decreased among medically induced preterm births but not among spontaneous preterm births.
What Do These Findings Mean?
These findings indicate that in Scotland between 1980 and 2004, increases in spontaneous and medically induced preterm births contributed equally to the rising rate of preterm births. Importantly, they also show that the increase in induced preterm births helped to reduce stillbirths and neonatal and perinatal deaths, a finding that supports the criteria that clinicians currently use to decide whether to induce an early birth. Nevertheless, preterm births still account for two-thirds of all stillbirths, neonatal deaths, and extended neonatal stays in hospital and thus cause considerable suffering and greatly increase the workload in neonatal units. The rates of such births consequently need to be reduced and, for Scotland at least, ways will have to be found to reduce the rates of both spontaneous and induced preterm births to achieve this goal while continuing to identify those sick babies who need to be delivered early to give them the best chance of survival.
Additional Information
Please access these Web sites via the online version of this summary at
Tommys is a nonprofit organization that funds research and provides information on the causes and prevention of miscarriage, premature birth, and stillbirth
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
The Nemours Foundation, another nonprofit organization for child health, also provides information on premature babies (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on maternal and infant health (in English and Spanish)
The US National Women's Health Information Center has detailed information about pregnancy, including a section on pregnancy complications
MedlinePlus provides links to other information on premature babies and to information on pregnancy (in English and Spanish)
PMCID: PMC2740823  PMID: 19771156
21.  Prohypertensive Effect of Gestational Personal Exposure to Fine Particulate Matter. Prospective Cohort Study in Non-smoking and Non-obese Pregnant Women 
Cardiovascular Toxicology  2012;12(3):216-225.
Exposure to fine particulate matter (PM) is a recognized risk factor for elevated blood pressure (BP) and cardiovascular disease in adults, and this prospective cohort study was undertaken to evaluate whether gestational exposure to PM2.5 has a prohypertensive effect. We measured personal exposure to fine particulate matter (PM2.5) by personal air monitoring in the second trimester of pregnancy among 431 women, and BP values in the third trimester were obtained from medical records of prenatal care clinics. In the general estimating equation model, the effect of PM2.5 on BP was adjusted for relevant covariates such as maternal age, education, parity, gestational weight gain (GWG), prepregnancy BMI, environmental tobacco smoke (ETS), and blood lead level. Systolic blood pressure (SBP) increased in a linear fashion across a dosage of PM2.5 and on average augmented by 6.1 mm Hg (95% CI, 0.6–11.6) with log unit of PM2.5 concentration. Effects of age, maternal education, prepregnancy BMI, blood lead level, and ETS were insignificant. Women with excessive gestational weight gain (>18 kg) had higher mean SBP parameters by 5.5 mmHg (95% CI, 2.7–8.3). In contrast, multiparous women had significantly lower SBP values (coeff. = −4.2 mm Hg; 95% CI, −6.8 to −1.6). Similar analysis performed for diastolic blood pressure (DBP) has demonstrated that PM2.5 also affected DBP parameters (coeff. = 4.1; 95% CI, −0.02 to 8.2), but at the border significance level. DBP values were positively associated with the excessive GWG (coeff. = 2.3; 95% CI, 0.3–4.4) but were inversely related to parity (coeff. = −2.7; 95% CI, −4.6 to −0.73). In the observed cohort, the exposure to fine particulate matter during pregnancy was associated with increased maternal blood pressure.
PMCID: PMC3404286  PMID: 22328329
Blood pressure; Exposure to fine particulate matter; Pregnancy; Gestational weight gain; Prepregnancy ponderal index; Environmental tobacco smoke
22.  Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial 
PLoS Medicine  2012;9(5):e1001217.
Diana Gibb and colleagues investigate the effect of in utero tenofovir exposure by analyzing the pregnancy and infant outcomes of HIV-infected women enrolled in the DART trial.
Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)–recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure.
Methods and Findings
Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models.
382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0–4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12–38) months. From mothers' ART, 62/9/111 infants had no/20%–89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75–212) days. Overall, 14 infants died at median (IQR) age 9 (3–23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens.
Overall 1-year 5% infant mortality was similar to the 2%–4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children.
Trial registration ISRCTN13968779
Please see later in the article for the Editors' Summary
Editors' Summary
Currently, about 34 million people (mostly in low- and middle-income countries) are infected with HIV, the virus that causes AIDS. At the beginning of the epidemic, more men than women were infected with HIV but now about half of all people living with HIV/AIDS are women, most of who became infected through unprotected sex with an infected partner. In sub-Saharan Africa alone, 12 million women are HIV-positive. Worldwide, HIV/AIDS is the leading cause of death among women of child-bearing age. Moreover, most of the 400,000 children who become infected with HIV every year acquire the virus from their mother during pregnancy or birth, or through breastfeeding, so-called mother-to-child transmission (MTCT). Combination antiretroviral therapy (ART)—treatment with cocktails of powerful antiretroviral drugs—reduces HIV-related illness and death among women, and ART given to HIV-positive mothers during pregnancy and delivery and to their newborn babies greatly reduces MTCT.
Why Was This Study Done?
Because of ongoing international efforts to increase ART coverage, more HIV-positive women in Africa have access to ART now than ever before. However, little is known about pregnancy outcomes among HIV-infected African women taking ART throughout pregnancy for their own health or about the long-term outcomes of their offspring. In particular, few studies have examined the effect of taking tenofovir (an antiretroviral drug that is now recommended as part of first-line ART) throughout pregnancy. Tenofovir readily crosses from mother to child during pregnancy and, in animal experiments, high doses of tenofovir given during pregnancy caused bone demineralization (which weakens bones), kidney problems, and impaired growth among offspring. In this study, the researchers analyze data collected on pregnancy and infant outcomes among Ugandan and Zimbabwean HIV-positive women who took ART throughout pregnancy in the Development of AntiRetroviral Therapy in Africa (DART) trial. This trial was designed to test whether ART could be safely and effectively delivered in Africa without access to the expensive laboratory tests that are routinely used to monitor ART toxicity and efficacy in developed countries.
What Did the Researchers Do and Find?
The pregnancy outcomes of 302 women who became pregnant during the DART trial and information on birth defects among their babies were collected as part of the DART protocol; information on the survival, growth, and development of the infants born to these women was collected in a separate infant study. Most of the women who became pregnant were taking tenofovir-containing ART before and throughout their pregnancies. 58% of the pregnancies resulted in a live birth, 7% resulted in a stillbirth (birth of a dead baby at any time from 22 weeks gestation to the end of pregnancy), and 35% resulted in a termination or miscarriage (before 22 weeks gestation). Of the 226 live births, seven infants died within 2 weeks and seven had birth defects. Similar proportions of the infants exposed and not exposed to tenofovir during pregnancy died soon after birth or had birth defects. Of the 182 surviving infants who were enrolled in the infant study, 14 subsequently died at an average age of 9 months, giving a 1-year mortality of 5%. None of the surviving children who were tested (172 infants) were HIV infected. No bone fractures or major kidney problems occurred during follow-up and prebirth exposure to tenofovir in utero had no effect on growth or weight gain at 2 years (in contrast to a previous US study).
What Do These Findings Mean?
By showing that prebirth tenofovir exposure does not affect pregnancy outcomes or increase birth defects, growth abnormalities, or kidney problems, these findings support the use of tenofovir-containing ART during pregnancy among HIV-positive African women, and suggest that it could also be used to prevent women of child-bearing age acquiring HIV-infection heterosexually. Notably, the observed 5% 1-year infant mortality is similar to the 2%–4% infant mortality normally seen in the region. The absence of HIV infection among the infants born to the DART participants is also encouraging. However, this is a small study (only 111 infants were exposed to tenofovir throughout pregnancy) and women were not randomly assigned to receive tenofovir-containing ART. Consequently, more studies are needed to confirm that tenofovir exposure during pregnancy does not affect pregnancy outcomes or have any long-term effects on infants. Such studies are essential because the use of tenofovir as a treatment for women who are HIV-positive is likely to increase and tenofovir may also be used in the future to prevent HIV acquisition in HIV-uninfected women.
Additional Information
Please access these Web sites via the online version of this summary at
Information is available from the US National Institute of Allergy and infectious diseases on all aspects of HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment (in several languages)
Information is available from Avert, an international AIDS nonprofit on many aspects of HIV/AIDS, including detailed information on HIV/AIDS treatment and care, women, HIV and AIDS, children, HIV and AIDS, and on HIV/AIDS and pregnancy (some information in English and Spanish); personal stories of women living with HIV are available
More information about the DART trial is available
Additional patient stories about living with HIV/AIDS are available through the nonprofit website Healthtalkonline
PMCID: PMC3352861  PMID: 22615543
23.  Post-neonatal Mortality, Morbidity, and Developmental Outcome after Ultrasound-Dated Preterm Birth in Rural Malawi: A Community-Based Cohort Study 
PLoS Medicine  2011;8(11):e1001121.
Using data collected as a follow-up to a randomized trial, Melissa Gladstone and colleagues show that during the first two years of life, infants born preterm in southern Malawi are disadvantaged in terms of mortality, growth, and development.
Preterm birth is considered to be associated with an estimated 27% of neonatal deaths, the majority in resource-poor countries where rates of prematurity are high. There is no information on medium term outcomes after accurately determined preterm birth in such settings.
Methods and Findings
This community-based stratified cohort study conducted between May–December 2006 in Southern Malawi followed up 840 post-neonatal infants born to mothers who had received antenatal antibiotic prophylaxis/placebo in an attempt to reduce rates of preterm birth (APPLe trial ISRCTN84023116). Gestational age at delivery was based on ultrasound measurement of fetal bi-parietal diameter in early-mid pregnancy. 247 infants born before 37 wk gestation and 593 term infants were assessed at 12, 18, or 24 months. We assessed survival (death), morbidity (reported by carer, admissions, out-patient attendance), growth (weight and height), and development (Ten Question Questionnaire [TQQ] and Malawi Developmental Assessment Tool [MDAT]). Preterm infants were at significantly greater risk of death (hazard ratio 1.79, 95% CI 1.09–2.95). Surviving preterm infants were more likely to be underweight (weight-for-age z score; p<0.001) or wasted (weight-for-length z score; p<0.01) with no effect of gestational age at delivery. Preterm infants more often screened positively for disability on the Ten Question Questionnaire (p = 0.002). They also had higher rates of developmental delay on the MDAT at 18 months (p = 0.009), with gestational age at delivery (p = 0.01) increasing this likelihood. Morbidity—visits to a health centre (93%) and admissions to hospital (22%)—was similar for both groups.
During the first 2 years of life, infants who are born preterm in resource poor countries, continue to be at a disadvantage in terms of mortality, growth, and development. In addition to interventions in the immediate neonatal period, a refocus on early childhood is needed to improve outcomes for infants born preterm in low-income settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Being born at term in Africa is not necessarily straightforward. In Malawi, 33 of every 1,000 infants born die in the first 28 days after birth; the lifetime risk for a mother dying during or shortly after pregnancy is one in 36. The comparable figures for the United Kingdom are three infants dying per 1,000 births and a lifetime risk of maternal death of one in 4,700. But for a baby, being born preterm is even more risky and the gap between low- and high-income countries widens still further. According to a World Health Organization report in 2010, a baby born at 32 weeks of gestation (weighing around 2,000 g) in Africa has little chance of survival, while the chances of survival for a baby born at 32 weeks in North America or Europe are similar to one born at term. There are very few data on the longer term outcomes of babies born preterm in Africa and there are multiple challenges involved in gathering such information. As prenatal ultrasound is not routinely available, gestational age is often uncertain. There may be little routine follow-up of preterm babies as is commonplace in high-income countries. Data are needed from recent years that take into account both improvements in perinatal care and adverse factors such as a rising number of infants becoming HIV positive around the time of birth.
Why Was This Study Done?
We could improve outcomes for babies born preterm in sub-Saharan Africa if we understood more about what happens to them after birth. We cannot assume that the progress of these babies will be the same as those born preterm in a high-income country, as the latter group will have received different care, both before and after birth. If we can document the problems that these preterm babies face in a low-income setting, we can consider why they happen and what treatments can be realistically tested in this setting. It is also helpful to establish baseline data so that changes over time can be recorded.
The aim of this study was to document four specific outcomes up to the age of two years, on which there were few data previously from rural sub-Saharan Africa: how many babies survived, visits to a health center and admissions to the hospital, growth, and developmental delay.
What Did the Researchers Do and Find?
The researchers examined a group of babies that had been born to mothers who had taken part in a randomized controlled trial of an antibiotic to prevent preterm birth. The trial had previously shown that the antibiotic (azithromycin) had no effect on how many babies were born preterm or on other measures of the infants' wellbeing, and so the researchers followed up babies from both arms of the trial to look at longer term outcomes. From the original group of 2,297 women who took part in the trial, they compared 247 infants born preterm against 593 term infants randomly chosen as controls, assessed at 12, 18, or 24 months. The majority of the preterm babies who survived past a month of age (all but ten) were born after 32 weeks of gestation. Compared to the babies born at term, the infants born preterm were nearly twice as likely to die subsequently in the next two years, were more likely to be underweight (a third were moderately underweight), and to have higher rates of developmental delay. The commonest causes of death were gastroenteritis, respiratory problems, and malaria. Visits to a health center and admissions to hospital were similar in both groups.
What Do these Findings Mean?
This study documents longer term outcomes of babies born preterm in sub-Saharan Africa in detail for the first time. The strengths of the study include prenatal ultrasound dating and correct adjustment of follow-up age (which takes into account being born before term). Because the researchers defined morbidity using routine health center attendances and self-report of illnesses by parents, this outcome does not seem to have been as useful as the others in differentiating between the preterm and term babies. Better means of measuring morbidity are needed in this setting.
In the developed world, there is considerable investment being made to improve care during pregnancy and in the neonatal period. This investment in care may help by predicting which mothers are more likely to give birth early and preventing preterm birth through drug or other treatments. It is to be hoped that some of the benefit will be transferable to low-income countries. A baby born at 26 weeks' gestation and admitted to a neonatal unit in the United Kingdom has a 67% chance of survival; preterm babies born in sub-Saharan Africa face a starkly contrasting future.
Additional Information
Please access these Web sites via the online version of this summary at
UNICEF presents useful statistics on mother and child outcomes
The World Health Organization has attempted to analyse preterm birth rates worldwide, including mapping the regional distribution and has also produced practical guides on strategies such as Kangaroo Mother Care, which can be used for the care of preterm infants in low resource settings
Healthy Newborn Network has good information on initiatives taking place to improve neonatal outcomes in low income settings
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on research being conducted into preterm birth
Tommy's is a nonprofit organization that funds research and provides information on the risks and causes of premature birth
PMCID: PMC3210771  PMID: 22087079
The Science of the total environment  2011;409(24):5205-5209.
Prenatal Paracetamol (Acetaminophen) has been associated with increased risk of allergic disease in early childhood, an association that could be due to increased altered susceptibility induced by air pollutants. The main goal of the study was to test the hypothesis that prenatal Paracetamol exposure increases the risk of developing eczema in early childhood and that this association is stronger for children who are exposed prenatally to higher concentrations of fine particulate matter (PM2.5). The study sample consisted of 322 women recruited from January 2001 to February 2004 in the Krakow inner city area who gave birth to term babies and completed 5-year follow-up. Paracetamol use in pregnancy was collected by interviews and prenatal personal exposure to over 48 hours was measured in all recruited women in the second trimester of PM2.5 pregnancy. After delivery, every three months in the first 24 months of the newborn’s life and every 6 months later, a detailed standardized face-to-face interview on the infant’s health was administered to each mother by a trained interviewer. During the interviews at each of the study periods after birth, a history of eczema was recorded.
By Cox proportional hazard regression, prenatal exposure to Paracetamol increased the risk of eczema by 20% and PM2.5 by 6%, albeit non significantly. However, the the joint exposure to Paracetamol and higher prenatal PM2.5 was significant and doubled the risk of eczema symptoms (HR = 2.07, 95%CI: 1.01 – 4.34). The findings suggest that even very small doses of Paracetamol in pregnancy may affect the occurrence of allergy outcomes such as eczema in early childhood but only at the co-exposure to higher fine particulate matter.
PMCID: PMC3428593  PMID: 21962593
birth cohort study; eczema; children; acetaminophen; pregnancy; prenatal fine particulate matter
25.  Associations of maternal fish intake during pregnancy and breastfeeding duration with attainment of developmental milestones in early childhood: a study from the Danish National Birth Cohort2 
Few studies have examined the overall effect of maternal fish intake during pregnancy on child development or examined whether the developmental benefits of maternal fish intake are greater in infants breastfed for a shorter duration.
We aimed to study associations of maternal prenatal fish intake and breastfeeding duration with child developmental milestones.
We studied 25 446 children born to mothers participating in the Danish National Birth Cohort, a prospective population-based cohort study including pregnant women enrolled between 1997 and 2002. Mothers reported child development by a standardized interview, which we used to generate developmental scores at ages 6 and 18 mo. We used multivariate cumulative ordinal logistic regression to evaluate the odds of higher developmental scores associated with maternal fish intake and breastfeeding, after adjustment for child age, sex, and growth; maternal size and pregnancy characteristics; and parental education and social status.
Higher maternal fish intake and greater duration of breast-feeding were associated with higher child developmental scores at 18 mo [odds ratio: 1.29 (95% CI: 1.20, 1.38) for the highest versus the lowest quintile of fish intake, and 1.28 (1.18, 1.38) for breast-feeding for ≥10 mo compared with breastfeeding for ≤1 mo]. Associations were similar for development at 6 mo. Associations of fish intake with child development did not differ by breastfeeding duration.
Maternal fish intake during pregnancy and the duration of breastfeeding are independently associated with better early child development. Future research and consumption guidelines, incorporating nutritional benefits as well as contaminant risks, should consider the overall effect of prenatal fish consumption on child development.
PMCID: PMC2875187  PMID: 18779297

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