A prospective cohort study of pregnancy risk factors and birth outcomes in Aboriginal women

Background

Aboriginal women have been identified as having poorer pregnancy outcomes than other Canadian women, but information on risk factors and outcomes has been acquired mostly from retrospective databases. We compared prenatal risk factors and birth outcomes of First Nations and Métis women with those of other participants in a prospective study.

Methods

During the 12-month period from July 1994 to June 1995, we invited expectant mothers in all obstetric practices affiliated with a single teaching hospital in Edmonton to participate. Women were recruited at their first prenatal visit and followed through delivery. Sociodemographic and clinical data were obtained by means of a patient questionnaire, and microbiological data were collected at 3 points during gestation: in the first and second trimesters and during labour. Our primary outcomes of interest were low birth weight (birth weight less than 2500 g), prematurity (birth at less than 37 weeks'' gestation) and macrosomia (birth weight greater than 4000 g).

Results

Of the 2047 women consecutively enrolled, 1811 completed the study through delivery. Aboriginal women accounted for 70 (3.9%) of the subjects who completed the study (45 First Nations women and 25 Métis women). Known risk factors for adverse pregnancy outcome were more common among Aboriginal than among non-Aboriginal women, including previous premature infant (21% v. 11%), smoking during the current pregnancy (41% v. 13%), presence of bacterial vaginosis in midgestation (33% v. 13%) and poor nutrition as measured by meal consumption. Although Aboriginal women were less likely than non-Aboriginal women to have babies of low birth weight (odds ratio [OR] 1.46, 95% confidence interval [CI] 0.52–4.15) or who were born prematurely (OR 1.45, 95% CI 0.57–3.72) and more likely to have babies with macrosomia (OR 2.04, 95% CI 1.03–4.03), these differences were lower and statistically nonsignificant after adjustment for smoking, cervicovaginal infection and income (adjusted OR for low birth weight 0.85, 95% CI 0.19–3.78; for prematurity 0.90, 95% CI 0.21–3.89; and for macrosomia 2.12, 95% CI 0.84-5.36).

Interpretation

After adjustment for potential confounding factors, we found no statistically significant relation between Aboriginal status and birth outcome.It is generally recognized that Aboriginal women experience poorer birth outcomes than other North American women, including higher rates of stillbirth,¹ low-birth-weight infants^1,2,3 and prematurity.^2,3 Although significant efforts have been made to reduce Aboriginal infant mortality rates, these rates remain higher than for other infants in both Canada⁴ and the United States.⁵ Little is known about the reasons for differences in birth outcomes, although social, economic, medical and prenatal care factors have been suggested. Recent publications, based on retrospective analyses of large databases, have confirmed disparities in birth outcomes between Aboriginal and all other groups,^3,6,7 but there is a paucity of prospective data. In addition, although the term “Aboriginal” refers to a heterogeneous population comprising First Nations people, Métis and Inuit, there are few comparisons between specific Aboriginal groups or of Aboriginal groups with the general population.We report here the results of a prospective study in a general obstetric population, comparing birth outcomes and known pregnancy risk factors of Aboriginal women with those of non-Aboriginal Canadian women. In addition to well-recognized socioeconomic and reproductive risk factors, we investigated the prevalence of maternal cervicovaginal infections, which have been increasingly linked to prematurity.^8,9     

Effects of grandmothers' smoking in pregnancy on birth weight: intergenerational cohort study

Objective To investigate the influences on birth weight of maternal smoking during pregnancy across generations.Design Intergenerational cohort study.Participants Members of the 1958 birth cohort and their offspring and mothers.Setting England, Scotland, and Wales.Main outcome measure Birth weight.Results Information on grandmothers'' smoking during pregnancy was available for 9028 singleton offspring of 4302 female cohort members. Assuming heritable transmission through the intergenerational association, grandmothers'' smoking was predicted to result in a 34 g reduction (95% confidence interval -41 g to -28 g) in the birth weight of grandchildren. Random effects models showed a negative association between grandmothers'' smoking and birth weight of grandchildren (β regression coefficient -24 g, -50 g to 3 g), but this effect was eliminated after adjustment for maternal smoking (0 g, -26 g to 26 g).No association was evident among the offspring of non-smoking mothers (n = 6105; 14 g, -17 g to 46 g), and after adjustment for maternal birth weight, adult height and body mass index, grandmothers'' smoking was positively associated with the birth weight of grandchildren (45 g, 10 g to 80 g).Conclusion Deficits in mothers'' birth weight attributable to their mother smoking was not evident in the grandchildren.     

Application of non-invasive biomarkers in a birth cohort follow-up in relation to respiratory health outcome

Asthma-related symptoms can manifest in children during the early years, but only some of the children will develop the disease. This feasibility study showed that it is possible to apply non-invasive markers (in urine, exhaled nitric oxide (FENO) and exhaled breath condensate (EBC)) in 3-year-old children, and evaluated the biomarkers in relation to health outcomes and potential modifiers. FENO was correlated with respiratory allergy, and was borderline significantly correlated with wheezing, but not with the asthma predictive index (mAPI). EBC pH and urinary 8-oxo-deoxyguanosine were not significantly correlated with these clinical outcomes. An EBC proteolytic peptide pattern was developed, which could distinguish between mAPI-positive and -negative children. Non-invasive biomarkers may become a promising tool for investigating respiratory health in children but further research is needed.     

Pediatric paradox: heterogeneity in the birth cohort

Comparisons of birth-weight-specific infant mortality indicate that low-birth-weight African American infants have lower mortality than low-birth-weight European American infants despite higher infant mortality overall-the "pediatric paradox." One explanation is heterogeneity in birth weight. Analyses of African American and European American births suggest that birth cohorts consist of two heterogeneous subpopulations. One appears to account for normal births, whereas the other may consist of compromised births. Estimates of infant mortality indicate that the compromised subpopulation has higher overall mortality but lower birth-weight-specific mortality. We attribute lower birth-weight-specific infant mortality in the compromised subpopulation to higher rates of fetal loss. Compared to European American birth cohorts, African American birth cohorts have (1) higher birth-weight-specific mortality in the normal subpopulation, (2) larger compromised subpopulations, and (3) lower birth-weight-specific mortality in the compromised subpopulation. Consequently, the pediatric paradox is attributable to greater rates of compromised pregnancies and higher fetal losses among African Americans.     

Associations between oxidative parameters in pregnancy and birth anthropometry in a cohort of women and children in rural Bangladesh: the MINIMat-cohort

Oxidative stress is suggested as a potential mechanism in impaired foetal growth, smaller birth size and thus subsequently adult chronic diseases. We have investigated associations between oxidative stress in pregnancy and birth anthropometry (weight, height, head and chest circumferences). In the MINIMat-trial (Maternal and Infant Nutrition Interventions, Matlab) in rural Bangladesh, free 8-iso-prostaglandin F(2α) (lipid peroxidation) was analysed in pregnancy week 14 and 30 and 8-Hydroxy-2 -Deoxyguanosine (DNA oxidation) in week 19. We found that higher levels of lipid peroxidation in early pregnancy were associated with larger infant size (birth length and chest circumference). In late pregnancy, no clear pattern of associations was found. Increasing level of DNA oxidation was associated with lower birth length in girls but no other associations were found. In conclusion, a higher level of lipid peroxidation in early (but not late) pregnancy was associated with a favourable larger birth size suggesting that timing of lipid peroxidation is of importance.     

Oxidative stress early in pregnancy and pregnancy outcome

The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF(2alpha) (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.     

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and the risk of selected birth defects: a prospective cohort study

Background

Since use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results of human studies on the teratogenic risks of NSAIDs are inconsistent. Therefore, we evaluated the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs.

Methods and Findings

We used data on 69,929 women enrolled in the Norwegian Mother and Child Cohort Study between 1999 and 2006. Data on NSAID exposure were available from a self-administered questionnaire completed around gestational week 17. Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. Only birth defects suspected to be associated with NSAID exposure based upon proposed teratogenic mechanisms and previous studies were included in the multivariable logistic regression analyses. A total of 3,023 women used NSAIDs in gestational weeks 0–12 and 64,074 women did not report NSAID use in early pregnancy. No associations were observed between overall exposure to NSAIDs during pregnancy and the selected birth defects separately or as a group (adjusted odds ratio 0.7, 95% confidence interval 0.4–1.1). Associations between maternal use of specific types of NSAIDs and the selected birth defects were not found either, although an increased risk was seen for septal defects and exposure to multiple NSAIDs based on small numbers (2 exposed cases; crude odds ratio 3.9, 95% confidence interval 0.9–15.7).

Conclusions

Exposure to NSAIDs during the first 12 weeks of gestation does not seem to be associated with an increased risk of the selected birth defects. However, due to the small numbers of NSAID-exposed infants for the individual birth defect categories, increases in the risks of specific birth defects could not be excluded.     

Drugs in pregnancy: the effects on mother and her progeny

Drug abuse during pregnancy is a growing problem in all developed countries all over the world. The drugs easily cross the placental barrier into the fetal body and are present also in the maternal milk. Therefore, it may affect the development of the child pre- as well as postnatally. The effects of prenatal drug exposure are long-lasting and persist until adulthood. The present review summarizes the clinical and experimental evidence showing how opioids and psychostimulants can affect maternal behavior of drug-abusing mother and the development of their offspring.     

Hirschsprung disease in a large birth cohort

The incidence of Hirschsprung disease was studied in a series of almost 700,000 consecutive livebirths in British Columbia from 1964-1982, by means of the records of a health surveillance registry that uses multiple sources of ascertainment. The estimated liveborn incidence rate for Hirschsprung disease was 1 in 4,417 livebirths (156 cases out of 689,118 livebirths). Data pertaining to sex ratio, additional anomalies, recurrence, and mortality were also analyzed over the caseload period 1952 to 1983. A total of 29.8% of cases had some additional anomaly--the majority being nonregional anomalies in other systems or more distantly in the gastrointestinal tract. Cardiovascular and gastrointestinal anomalies not a direct consequence of Hirschsprung disease were the most frequent additional anomalies found, occurring in 10 and 12 of 178 cases, respectively. Sensorineural anomalies were also frequent, occurring in 12 of 178 cases. Clinical implications arising from the study regarding the neonatal assessment of infants with these anomalies are discussed.     

Post-neonatal mortality, morbidity, and developmental outcome after ultrasound-dated preterm birth in rural Malawi: a community-based cohort study

Background

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.

Conclusions

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     

Antidepressants and pregnancy: risks and benefits for the mother and child

Depression, anxiety disorders, anorexia nervosa and bulimia, all indications for antidepressant use, are common disorders in women of childbearing age. Nevertheless, antidepressant use during the gestational period remains a controversial topic. Given that 50 % of pregnancies are unplanned, the safety of antidepressants during the first trimester of pregnancy, a critical period for foetal development, has become a major public health concern. Until now, most studies suggest that physicians may often under-prescribe or discontinue antidepressants at the time of conception and during pregnancy. This may be a consequence of the concern over the safety of these agents in pregnant women and the risks they may pose to the foetus. In fact, recent studies and warnings from Health Canada and the US Food and Drug Administration have reinforced this uncertainty regarding the adverse effects of antidepressant use on the foetus. On the other hand, discontinuation of antidepressant use during pregnancy was also recently associated with maternal relapse of depression and withdrawal symptoms, which is not optimal for the mother and her foetus. Consequently, women who wish to become pregnant and who suffer from psychiatric disorders are faced with the difficult task of deciding whether to continue or discontinue their antidepressant during pregnancy. At this time, it appears important to take into account all evidence-based data to evaluate the risks/benefits of using antidepressants during the gestational period in order to help mothers make the best choice for themselves, and their infants.     

Birth-weight-specific infant and neonatal mortality: effects of heterogeneity in the birth cohort

Birth-weight-specific infant mortality is examined using a novel statistical procedure, parametric mixtures of logistic regressions. The results indicate that birth cohorts are composed of two or more subpopulations that are heterogeneous with respect to infant mortality. One subpopulation appears to account for the "normal" process of fetal development, while the other, which accounts for the majority of births at both low and high birth weights, may represent fetuses that were "disturbed" during development. Surprisingly, estimates of neonatal and infant mortality indicate that the "disturbed" subpopulation has lower birth-weight-specific mortality, although overall crude mortality rates are higher for this subpopulation. It is hypothesized that this is due to high rates of fetal loss among the "disturbed" subpopulation, resulting in a highly selected group at birth. The heterogeneity identified in the birth cohort could be responsible for recent decelerations in the decline in infant mortality, and might be the cause of unexplained ethnic differences in birth-weight-specific infant mortality. The novel statistical methodology developed here has broad application within human biology. In particular, it could be used in any context where parametric mixture modeling is applied, such as complex segregation analysis.     

Spontaneous premature birth in twin pregnancy.

Factors associated with spontaneous premature birth were investigated in 459 consecutive twin deliveries at this hospital. Low maternal age, low parity, and zygosity were significantly related to the incidence of this complication. The number of previous abortions, sex combinations and related birth order, and mode of presentation of the first twin were not related to the incidence of spontaneous premature delivery. We conclude that apart from low maternal age and low parity there are no obvious factors that would permit early identification of twin pregnancies at risk from spontaneous premature birth.     

Risk of premature birth in multifetal pregnancy.

The risk of preterm delivery (< 37 weeks of gestation) is approximately nine times higher in women with multifetal pregnancies than in women with singleton pregnancies. However, it is possible that the risk will vary according to gestational week. To assess the risk of premature birth within 1 week by gestational age among multifetal pregnancies and compare the estimated risk with that of singleton pregnancies, we analyzed 6,036,475 infants born in singleton pregnancies and 90,887 infants born in multifetal pregnancies in Japan (> or =22 weeks) over the 5-year period 1989-1993. An estimate of the risk of birth within 1 week at gestational week n was obtained by dividing the number of infants delivered at gestational week n by the number of infants delivered at or beyond gestational week n. The risk at 22 weeks was 0.9 per 1000 fetuses for singleton pregnancies and 5.0 per 1000 for multifetal pregnancies. The risk remained relatively stable until 27 weeks of gestation, then sharply increased toward 36 weeks of gestation in both singleton and multifetal pregnancies. The odds ratio for birth within 1 week for fetuses of multifetal pregnancies compared with fetuses of singleton pregnancies was 5.9 (95% CI, 5.4-6.5) at 22 weeks of gestation, increasing gradually with increasing gestational age until 33 weeks of gestation (13.7; 95% CI, 13.1-14.2) but declining thereafter to 8.8 (95% CI, 8.6-8.9) at 36 weeks of gestation. Results of data analysis for each year of the 5-year period did not differ substantially.     

Embryo quality: the missing link between pregnancy sickness and pregnancy outcome

Pregnancy sickness is widespread yet its etiology is poorly understood. It is almost certainly endocrine in origin and most likely a product of placental hormones, with human chorionic gonadotropin being the strongest candidate. It has long been known that greater levels of nausea and vomiting during pregnancy are associated with a lower incidence of spontaneous abortion, yet the causal mechanisms remain unclear. One current popular explanation is that nausea and vomiting during pregnancy is fetoprotective, inducing aversions to foods, especially meat, dairy and seafoods, which may carry toxins, pathogens or mutagens. However, most spontaneous abortions arise from genetic or epigenetic defects that are present at or near conception. Moreover, measurements of human chorionic gonadotropin (hCG) at the time of implantation, particularly its hyperglycosylated isoform, accurately predict subsequent spontaneous abortion. Thus the developmental fate of most embryos is fixed before the onset of the symptoms of pregnancy sickness. An alternative explanation for the link between pregnancy sickness and spontaneous abortion is the embryo quality hypothesis: high quality embryos are both more likely to produce the biochemical antecedents of pregnancy sickness and avoid spontaneous abortion. Recent work has shown that the link between pregnancy sickness and spontaneous abortion grows stronger with maternal age, dramatically so in mothers 35 or older. This reflects the parallel rise in the incidence of autosomal aneuploidies with maternal age. The link between pregnancy sickness and spontaneous abortion exists not because nausea and vomiting during pregnancy is fetoprotective, but because nausea and vomiting is an index of a high quality embryo. Pregnancy sickness is not adaptive per se, but the result of an antagonistic pleiotropy over thyroid function, where embryos use hCG to modulate maternal thyroid hormone production during gestation. Embryos benefit from the thyroid hormone production that is key to neurodevelopment, but produce maternal nausea and vomiting as a by-product. Pregnancy sickness, however, may still serve to protect embryo quality but by a different mechanism that posited under the MEPH. Embryo quality is protected by calibrating the dietary intake of a micronutrient – iodine – critical to neuromotor development. For most humans over most of our evolutionary history, iodine has been in short supply, and iodine deficiency is still the most common source of cognitive impairment across the globe. Thus it is of interest that the food aversions most commonly associated with pregnancy sickness, to meat, dairy and seafoods, are also the chief dietary sources of iodine. There is a further intriguing property about iodine: both too little and too much during early pregnancy are damaging to embryo brain development. Given that pregnancy sickness is closely linked to iodine intake and thyroid function (hypothyroidism is associated with lower levels of nausea and vomiting, hyperthyroidism with more), an obvious interpretation emerges. The previously described link between diet and pregnancy sickness – pregnancy sickness is less likely when plants and particularly corn/maize are the sole food staples – arises not because plant food staples are safe, as previously suggested, but because these foods are iodine poor and may, in addition, be goitrogenic. Pregnancy sickness, which reduces the dietary intake of iodine, is clearly maladaptive under conditions of iodine deficiency and hypothyroidism. Conversely, higher levels of pregnancy sickness induced by hyperthyroidism may protect embryos from the inimical effects of excessive dietary iodine during early gestation by reducing the intake of iodine rich foods.