Gestational Age at Birth and ‘Body-Mind’ Health at 5 Years of Age: A Population Based Cohort Study

Numerous studies have identified the effects of prematurity on the neonate’s physical health, however few studies have explored the effects of prematurity on both the physical and mental health of the child as they develop. Secondary analysis of data from the Millennium Cohort Study, a longitudinal study of infants (n = 18 818, born 2000–2002 in the United Kingdom) was performed. Effects of gestational age at birth on health outcomes at 5 years were measured using parental rating of their children’s general health and severity of behavior problems. The association between parent’s general health ratings and behavior problem ratings was low: 86% of those reporting serious behavior problems (5% of the sample, n = 764) rated their child as being in excellent, very good, or good health. Still, a gradient of increasing risk of poorer outcome with decreasing gestational age was observed for a composite health measure (poor/fair health and/or serious behavior problems), suggesting an association with prematurity for this composite assessment of health status. The greatest contribution to the childhood composite health measure at 5 years was for children born at 32–36 weeks gestation: population attributable fractions for having poor outcomes was 3.4% (Bonferroni-adjusted 95% confidence interval 1.1%–6.2%), compared to 1% (0.2–2.3) for birth at less than 32 weeks. Results suggest that preterm children, by school entry, are not only at high risk of physical health problems, but also of behavioral health problems. The recognition of, and response to comprehensive health and well-being outcomes related to prematurity are important in order to correctly plan and deliver adequate paediatric health services and policies.     

Psychosocial stress in pregnancy and its relation to low birth weight.

The relation of low birth weight to psychosocial stress in pregnancy was examined using a life events inventory and a state anxiety index. Two hundred and fifty women were randomly selected and interviewed three times during pregnancy and shortly after delivery. Twenty six were excluded. Of the remaining 224 women, nine miscarried, 195 had healthy term babies, and 20 gave birth to babies that were either premature or of low birth weight at term. Low birth weight and prematurity were significantly associated with objective major life events but not state anxiety. The occurrence of objective major life events in the third trimester may be important in precipitating preterm labour. Cigarette smoking was the best predictor and objective major life events the second best predictor of low birth weight. The result was not dependent on social class. These findings suggest that cigarette smoking may be an important mediator of stress on the fetus. Antenatal care should take greater account of stress in pregnancy, and social support systems should be evaluated.     

Low birth weight,intrauterine growth-retarded,and pre-term infants

Low birth weight, intrauterine growth retardation, and prematurity are overwhelming risk factors associated with infant mortality and morbidity. The lack of efficacious prenatal screening tests for these three outcomes illuminates the problems inherent in bivariate estimates of association. A biocultural strategy for research is presented, integrating societal and familial levels of analysis with the metabolic, immune, vascular, and neuroendocrine systems of the body. Policy decisions, it is argued, need to be based on this type of biocultural information in order to impact the difficult-to-change problems of low birth weight, intrauterine growth retardation, and prematurity. The analysis and writing of this study was funded, in part, by a grant from the National Institute of Child Health and Human Development (NICHD RO1 HD 20511). Troy D. Abell is associate professor of anthropology and adjunct associate professor of family medicine at the University of Oklahoma. His major interests are in the biocultural determinants of fetal growth and the epistemologic issues inherent in statistical reasoning in scientific inference and decision analysis.     

The COVID-19 pandemic and birth outcomes in 2020: The role of prenatal care and other channels

We use national birth data to assess the associations between the COVID-19 pandemic during 2020 and birth outcomes in Uruguay. Employing interrupted time series difference-in-differences techniques, we find mixed results, with some pregnancies showing increases in the likelihood of very preterm or very-low-weight births, and some others showing decreases in the incidence of moderate prematurity and moderate low birth weight. Adverse outcomes are more likely among women with low education, women with previous children, and with risk factors, such as smoking or being older than 34. We observe improvements in health at birth for children of non-smokers, women younger than 35, and women with no other children. We underscore the role of health care by showing that women in the private sector, who suffered the strongest contraction in face-to-face prenatal care use, experienced more adverse birth outcomes. Our results also suggest that the economic recession and an increased burden of childcare were behind the increases in preterm and very-low-weight births. Because pollution is an unlikely channel for the positive results, we hypothesize that for some pregnancies, the pandemic improved the intrauterine habitat by leading to a quieter and healthier lifestyle.     

Pregnancy outcome after gestational exposure to metronidazole: a prospective controlled cohort study

BACKGROUND: Metronidazole is an important antibacterial agent commonly used in women of reproductive age. Its use in pregnancy is a reason for concern for women and their health care providers. The objective was to examine the fetal safety of metronidazole. METHODS: The Israeli Teratogen Information Service prospectively collected and followed up 228 women exposed to metronidazole in pregnancy, 86.2% of whom with first-trimester exposure. Pregnancy outcome was compared with that of a control group, who were counseled during the same period for nonteratogenic exposure. RESULTS: There was no difference in the rate of major malformations between the groups (3/190; 1.6% [metronidazole] vs. 8/575; 1.4% [control], P = 0.739). The rate of major malformations did not differ between the groups even after including elective terminations of pregnancy due to prenatally diagnosed malformations (5/192; 2.6% [metronidazole] vs. 12/579; 2.1% [control], P = 0.777). A reduced neonatal birth weight was found in the metronidazole group compared with controls without significant differences in the rate of prematurity or in gestational age at delivery. The mean birth weight was lower in the metronidazole group when comparing the subgroup of term infants. CONCLUSIONS: This study confirms that metronidazole does not represent a major teratogenic risk in humans when used in the recommended doses.     

Perinatal Outcomes and Unconventional Natural Gas Operations in Southwest Pennsylvania

Unconventional gas drilling (UGD) has enabled extraordinarily rapid growth in the extraction of natural gas. Despite frequently expressed public concern, human health studies have not kept pace. We investigated the association of proximity to UGD in the Marcellus Shale formation and perinatal outcomes in a retrospective cohort study of 15,451 live births in Southwest Pennsylvania from 2007–2010. Mothers were categorized into exposure quartiles based on inverse distance weighted (IDW) well count; least exposed mothers (first quartile) had an IDW well count less than 0.87 wells per mile, while the most exposed (fourth quartile) had 6.00 wells or greater per mile. Multivariate linear (birth weight) or logistical (small for gestational age (SGA) and prematurity) regression analyses, accounting for differences in maternal and child risk factors, were performed. There was no significant association of proximity and density of UGD with prematurity. Comparison of the most to least exposed, however, revealed lower birth weight (3323 ± 558 vs 3344 ± 544 g) and a higher incidence of SGA (6.5 vs 4.8%, respectively; odds ratio: 1.34; 95% confidence interval: 1.10–1.63). While the clinical significance of the differences in birth weight among the exposure groups is unclear, the present findings further emphasize the need for larger studies, in regio-specific fashion, with more precise characterization of exposure over an extended period of time to evaluate the potential public health significance of UGD.     

Evaluation of the prothrombin gene polymorphism in patients with advanced retinopathy of prematurity

It has been reported recently that a common genetic variant in the 3'-untranslated region of the prothrombin gene is associated with a significant fraction of premature births. The purpose of this study is to evaluate the prothrombin gene polymorphism in a large cohort of patients with preterm birth and advanced retinopathy of prematurity. For this purpose, the leukocyte DNAs were analyzed for the mutation (20210A) in the 3'-untranslated region of the prothrombin gene by PCR amplification, followed by restriction analysis and DNA sequencing. Our extensive analysis revealed a normal genotype (GG) in all patients as well as controls. These results suggest that the common genetic variant in the 3'-untranslated region of the prothrombin gene is not associated with advanced retinopathy of prematurity. Although more patients' samples should be evaluated, this genetic test does not support a relationship between prothrombin gene mutation and retinopathy of prematurity.     

Pregnancy outcome of women exposed to azathioprine during pregnancy

BACKGROUND: Azathioprine (AZP) interferes with nucleic acid synthesis and is teratogenic in animals. In view of the paucity of information on the use of AZP during pregnancy we investigated this subject in a prospective, controlled, multicenter study. Our objective was too determine whether exposure to AZP during pregnancy increases the risk for major malformations and to determine the effect on pregnancy outcome. METHODS: Pregnant women on AZP who contacted one of seven teratogen information services were compared to a cohort of pregnant women who contacted two of the seven teratogen information services and took nonteratogenic treatments during their pregnancy. RESULTS: Follow-up was completed on 189 women in the AZP group and compared to 230 women in the control group. The rate of major malformations did not differ between groups with six neonates in each; the AZP rate was 3.5% and the control group rate was 3.0% (p = .775; OR 1.17; CI: 0.37, 3.69). The mean birth weight and gestational age were lower in the AZP group (2,995 g vs. 3,252 g [p = .001, difference of mean: 257, 95% CI: 106.3, 408.1] and 37.8 weeks vs. 39.1 weeks [p = .001, difference of mean: 1.3, 95% CI: .5, 2.0], respectively). The AZP group had more cases of prematurity (21.4% vs. 5.2% [p < .001; OR 4.0; 95% CI: 2.0, 8.06]) and low birth weight (23% vs. 6.0% [p < .001; OR 3.81; 95% CI: 2.0, 7.2]). CONCLUSIONS: These results suggest that AZP (50-100 mg/day) does not triple the rate of birth defects; however, it is associated with lower birth weight, gestational age, and prematurity. Larger studies are needed to confirm these observations.     

Atrazine and Pregnancy Outcomes: A Systematic Review of Epidemiologic Evidence

Atrazine (ATR) is a commonly used agricultural herbicide that has been the subject of epidemiologic studies assessing its relation to reproductive health problems. This review evaluates both the consistency and the quality of epidemiologic evidence testing the hypothesis that ATR exposure, at usually encountered levels, is a risk factor for birth defects, small for gestational age birth weight, prematurity, miscarriages, and problems of fetal growth and development. We followed the current methodological guidelines for systematic reviews by using two independent researchers to identify, retrieve, and evaluate the relevant epidemiologic literature on the relation of ATR to various adverse outcomes of birth and pregnancy. Each eligible paper was summarized with respect to its methods and results with particular attention to study design and exposure assessment, which have been cited as the main areas of weakness in ATR research. As a quantitative meta‐analysis was not feasible, the study results were categorized qualitatively as positive, null, or mixed. The literature on ATR and pregnancy‐related health outcomes is growing rapidly, but the quality of the data is poor with most papers using aggregate rather than individual‐level information. Without good quality data, the results are difficult to assess; however, it is worth noting that none of the outcome categories demonstrated consistent positive associations across studies. Considering the poor quality of the data and the lack of robust findings across studies, conclusions about a causal link between ATR and adverse pregnancy outcomes are not warranted.     

Executive functions of six-year-old boys with normal birth weight and gestational age

Impaired fetal development, reflected by low birth weight or prematurity, predicts an increased risk for psychopathology, especially attention deficit hyperactivity disorder (ADHD). Such effects cut across the normal range of birth weight and gestation. Despite the strength of existing epidemiological data, cognitive pathways that link fetal development to mental health are largely unknown. In this study we examined the relation of birth weight (>2500 g) and gestational age (37-41 weeks) within the normal range with specific executive functions in 195 Singaporean six-year-old boys of Chinese ethnicity. Birth weight adjusted for gestational age was used as indicator of fetal growth while gestational age was indicative of fetal maturity. Linear regression revealed that increased fetal growth within the normal range is associated with an improved ability to learn rules during the intra/extra-dimensional shift task and to retain visual information for short period of time during the delayed matching to sample task. Moreover, faster and consistent reaction times during the stop-signal task were observed among boys born at term, but with higher gestational age. Hence, even among boys born at term with normal birth weight, variations in fetal growth and maturity showed distinct effects on specific executive functions.     

Placental Barrier to Coagulation Factors: Its Relevance to the Coagulation Defect at Birth and to Haemorrhage in the Newborn

The placental barrier to coagulation factors was assessed by measuring their levels in maternal venous and neonatal umbilical arterial and venous blood and was found to be largely complete. Detailed coagulation assessments in a large number of term and premature neonates showed that term neonates had a mild coagulation deficiency at birth. Premature neonates had a more definite deficiency, which became more severe with increasing prematurity. Mortality in low birth weight premature infants was associated with a severe coagulation deficiency, and was frequently due to cerebral haemorrhage. It is suggested that the coagulation system of low birth weight infants should be assessed to enable prophylactic treatment of those with a severe deficiency.     

Changes in the association of low birth weight with socioeconomic status in Hawaii: 1970-1990

This study examines rates of low birth weight (LBW) in the state of Hawaii and changes in the association of LBW with socioeconomic status from 1970 to 1990. The analysis is based on aggregate data for census tracts. Rates of low birth weight were calculated for each census tract. Relative socioeconomic scores were calculated from average household income and years of education. The results show that (1) there was a decrease in the rate of low birth weight infants in Hawaii; and (2) that the correlation between socioeconomic status and low birth weight was substantially reduced, though a significant correlation remains. The paper suggests likely ceiling effects, but that the progressive public health policies and expansion of access to primary health care in Hawaii during this period played a major role in reducing the rate of low birth weight infants and in decreasing socioeconomic inequality on this important health indicator.     

Maternal transmission of type D simian retrovirus (SRV-2) in pigtailed macaques

Pregnant macaques were used as a natural model for maternal-infant transmission of SRV-2 retrovirus. Fifty-one pregnant females were placed into one of four virus/antibody groups. Nonviremic mothers produced 100% virus-negative offspring at birth. In contrast, viremic mothers produced offspring which were 17% virus-negative and 83% virus-positive at birth. SRV-2 infection occurred principally in utero by the transplacental route. Infants born to viremic mothers exhibited low birth weight, prematurity, high perinatal death, and increased incidence of SAIDS.     

Influence of common non-synonymous Toll-like receptor 4 polymorphisms on bronchopulmonary dysplasia and prematurity in human infants

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease and major risk factor for severe respiratory syncytial virus (RSV) infection among preterm infants. The Toll-like receptor 4 (TLR4) is involved in oxidative injury responses in the lungs. Two non-synonymous single nucleotide polymorphisms in the TLR4 gene have been associated with RSV infection in children. However, it is unclear to what extent this association is confounded by BPD or prematurity. In this study, we analyzed two population-based cohorts of preterm infants at risk for BPD as well as ethnicity-matched infants born at term, to test whether the TLR4 polymorphisms Asp299Gly (rs4986790) and Thr399Ile (rs4986791) are independently associated with BPD or premature birth. In a Canadian cohort (n = 269) composed of a majority of Caucasian preterm infants (BPD incidence of 38%), the TLR4-299 heterozygous genotype was significantly under-represented in infants without BPD (1.6% of infants versus 12% in infants with severe BPD) after adjusting for twins, ethnicity, gestational age, birth weight and gender (p = 0.014). This association was not replicated in a Finnish cohort (n = 434) of premature singletons or first-born siblings of Caucasian descent, although the incidence of BPD was substantially lower in this latter population (15%). We did not detect a significant association (>2-fold) between TLR4 genotypes and prematurity (p>0.05). We conclude that these TLR4 genotypes may have, at best, a modest influence on BPD severity in some populations of high-risk preterm infants. Further studies are warranted to clarify how clinical heterogeneity may impact genetic susceptibility to BPD.     

The Association of Neighborhood Social Capital and Ethnic (Minority) Density with Pregnancy Outcomes in the Netherlands

Background

Perinatal morbidity rates are relatively high in the Netherlands, and significant inequalities in perinatal morbidity and mortality can be found across neighborhoods. In socioeconomically deprived areas, ‘Western’ women are particularly at risk for adverse birth outcomes. Almost all studies to date have explained the disparities in terms of individual determinants of birth outcomes. This study examines the influence of neighborhood contextual characteristics on birth weight (adjusted for gestational age) and preterm birth. We focused on the influence of neighborhood social capital – measured as informal socializing and social connections between neighbors – as well as ethnic (minority) density.

Methods

Data on birth weight and prematurity were obtained from the Perinatal Registration Netherlands 2000–2008 dataset, containing 97% of all pregnancies. Neighborhood-level measurements were obtained from three different sources, comprising both survey and registration data. We included 3.422 neighborhoods and 1.527.565 pregnancies for the birth weight analysis and 1.549.285 pregnancies for the premature birth analysis. Linear and logistic multilevel regression was performed to assess the associations of individual and neighborhood level variables with birth weight and preterm birth.

Results

We found modest but significant neighborhood effects on birth weight and preterm births. The effect of ethnic (minority) density was stronger than that of neighborhood social capital. Moreover, ethnic (minority) density was associated with higher birth weight for infants of non-Western ethnic minority women compared to Western women (15 grams; 95% CI: 12,4/17,5) as well as reduced risk for prematurity (OR 0.97; CI 0,95/0,99).

Conclusions

Our results indicate that neighborhood contexts are associated with birth weight and preterm birth in the Netherlands. Moreover, ethnic (minority) density seems to be a protective factor for non-Western ethnic minority women, but not for Western women. This helps explain the increased risk of Western women in deprived neighborhoods for adverse birth outcomes found in previous studies.     

Maternal influenza immunization and reduced likelihood of prematurity and small for gestational age births: a retrospective cohort study

Background

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.

Conclusions

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     

Fetal programming of neuropsychiatric disorders

Starting from the Developmental Origins of Health and Disease (DOHaD) hypotheses proposed by David Barker, namely fetal programming, in the past years, there is a growing evidence of the major role played by epigenetic factors during the intrauterine life and the perinatal period. Furthermore, it has been assessed that these factors can affect the health status in infancy and even in adulthood. In this review, we focus our attention on the fetal programming of the brain, analyzing the most recent literature concerning the epigenetic factors that can influence the development of neuropsychiatric disorders such as bipolar disorders, major depressive disorders, and schizophrenia. The perinatal epigenetic factors have been divided in two main groups: maternal factors and fetal factors. The maternal factors include diet, smoking, alcoholism, hypertension, malnutrition, trace elements, stress, diabetes, substance abuse, and exposure to environmental toxicants, while the fetal factors include hypoxia/asphyxia, placental insufficiency, prematurity, low birth weight, drugs administered to the mother or to the baby, and all factors causing intrauterine growth restriction. A better comprehension of the possible mechanisms underlying the pathogenesis of these diseases may help researchers and clinicians develop new diagnostic tools and treatments to offer these patients a tailored medical treatment strategy to improve their quality of life. Birth Defects Research (Part C) 108:207–223, 2016. © 2016 Wiley Periodicals, Inc.     

Changes in the association of low birth weight with socioeconomic status in Hawaii: 1970–1990

Abstract

This study examines rates of low birth weight (LBW) in the state of Hawaii and changes in the association of LBW with socioeconomic status from 1970 to 1990. The analysis is based on aggregate data for census tracts. Rates of low birth weight were calculated for each census tract. Relative socioeconomic scores were calculated from average household income and years of education. The results show that (1) there was a decrease in the rate of low birth weight infants in Hawaii; and (2) that the correlation between socioeconomic status and low birth weight was substantially reduced, though a significant correlation remains. The paper suggests likely ceiling effects, but that the progressive public health policies and expansion of access to primary health care in Hawaii during this period played a major role in reducing the rate of low birth weight infants and in decreasing socioeconomic inequality on this important health indicator.