Effect of caffeine exposure during pregnancy on birth weight and gestational age

Epidemiologic studies have been unable to conclusively evaluate whether caffeine intake during pregnancy is associated with reduced birth weight and/or fetal growth restriction. The authors conducted a prospective, population-based cohort study to investigate the effect of caffeine on birth weight, gestational age, and birth weight standardized for gestational age (birth weight ratio). Of 953 women recruited in early pregnancy in Uppsala County, Sweden, from 1996 to 1998, 873 women delivering liveborn singleton infants were included in the analysis. Caffeine exposures were ascertained from in-person interviews at 6-12 and 32-34 completed gestational weeks, and maternal plasma was analyzed for cotinine levels as an indicator of smoking. Analysis of variance was used to estimate the effect of caffeine on birth weight, gestational age at delivery, and birth weight ratio after accounting for the effects of other covariates, such as maternal sociodemographic characteristics, plasma cotinine, and pregnancy symptoms. There were no associations between caffeine consumption and birth weight, gestational age, and birth weight ratio, neither when caffeine exposure was averaged from conception to the 32nd to 34th gestational weeks, nor when caffeine exposure was stratified by trimesters of pregnancy. These results do not support an association between moderate caffeine consumption and reduced birth weight, gestational age, or fetal growth.     

Maternal caffeine intake and intrauterine growth retardation.

This study estimates the effect of maternal caffeine consumption throughout pregnancy on fetal growth. We studied 2,714 women who delivered a liveborn infant between 1988 and 1991. Detailed information regarding coffee, tea, and soda drinking during the first and third trimesters of pregnancy was obtained. Average caffeine intake during month 1 of pregnancy was higher than for month 7 (72.4 vs 54.0 mg per day). Consumption of >300 mg caffeine per day during month 1 (adjusted odds ratio = 0.91; 95% confidence interval = 0.44--1.90) and during month 7 (adjusted odds ratio = 1.00; 95% confidence interval = 0.37--2.70) was not associated with intrauterine growth retardation. There was little evidence for any effect modification due to cigarette smoking on the caffeine associations. This study provides evidence that antenatal caffeine consumption has no adverse effect on fetal growth.     

Maternal age at birth and risk of breast cancer in daughters

Data from a large case-control study of breast cancer were examined to test the hypothesis that maternal age at the birth of female offspring is related to the incidence of breast cancer in daughters. Participants were between the ages of 20 and 54 at the time of the study. Based on results for 2,492 parous women who were newly diagnosed with breast cancer and 2,687 parous controls from the general population, a 15-year increase in maternal age was found to be associated with a 29% increase in the risk of breast cancer in daughters. Adjustment for the daughter's age, her own reproductive history, and other potential confounding factors yielded an estimate of 25% for this increase in risk (95% CI, 8% to 46%). The corresponding increase among 499 nulliparous cases and 457 nulliparous controls was 7%, which was not statistically significantly different in magnitude from the increase among parous women. These findings provide evidence for perinatal influences on the subsequent incidence of breast cancer during adulthood. Although specific mechanisms cannot be inferred directly, the results are consistent with the hypothesis that mutations in the genes of the human egg or sperm play a role in the etiology of breast cancer in female offspring.     

Maternal nutrition and spontaneous preterm birth.

Previous studies suggesting that maternal undernutrition increases the risk of preterm birth have suffered from several methodological shortcomings, including use of total gestational weight gain rather than net rate of gain in maternal tissue, inclusion of induced preterm deliveries, and error-prone gestational age measurements based solely on menstrual dates. The authors have attempted to overcome these shortcomings by investigating the potential etiologic roles of prepregnancy body mass index, net rate of maternal weight gain, height, and a number of other potential biological and sociodemographic determinants of spontaneous (i.e., noninduced) preterm birth in a cohort of 13,102 women with early ultrasound-confirmed gestational age who delivered at the Royal Victoria Hospital in Montreal, Quebec, Canada, between January 1, 1980 and March 31, 1989. Total weight gain, but not body mass index, was highly significantly associated with spontaneous preterm birth, averaging 14.6, 12.5, 9.9, and 9.1 kg, in women delivering at 37 or more, less than 37, less than 34, and less than 32 completed weeks, respectively. Although the relation persisted when weight gain was expressed as an overall rate, it disappeared when the analysis was based on net rate; mean net rates of gain were 0.28, 0.29, 0.27, and 0.27 kg/week, respectively. On the basis of multiple logistic regression analyses, significant determinants of birth at less than 37 weeks included maternal short stature; noncompletion of high school; unmarried status; smoking; diabetes; urinary tract infection within 2 weeks of delivery; prepregnancy hypertension; severe pregnancy-induced hypertension; and previous history of preterm delivery, low birth weight, or neonatal death. Most of these factors retained their significance for birth at less than 34 and less than 32 weeks. In fact, the effect of low maternal education was even stronger at these more severe "levels" of preterm birth. The authors conclude that prepregnancy weight-for-height and gestational weight gain are not important determinants of spontaneous preterm birth and that some previous studies have mistaken an effect of shortened gestation for its cause. Other biologic and social determinants, however, indicate priorities for future research and intervention.     

Classification of small-for-gestational age births: weight-by-gestation standards of second birth conditional on the size of the first

Percentiles of weight-by-gestational age were constructed for first and second births, based on linked sibship-data from the Medical Birth Registry of Norway. Standards were made for weight-by-gestational age of second births conditional on whether the first birth was small-for-gestational age (SGA) or large-for-gestational age (LGA). These standards were compared with the conventional, cross-sectional standard of all second births. The relevance of the conditional standards was assessed on the basis of perinatal mortality, using logistic regression analyses. When applying cross-sectional standards of second births, more than 30% of the births following a SGA first birth were classified as SGA, compared with only 1.7% following an LGA first births. The overall risk for a perinatal loss in second births following a SGA first birth was twice that among second births following a LGA first birth. When second births were themselves categorised as SGA or non-SGA using the cross-sectional standards, the mortality among the SGA second births was such that the risk was 4 to 5 times higher following LGA first births compared with SGA first births. When conditional standards were applied to define SGA among second births, the risk relation between the subgroups (defined by classification of first birth) corresponded to the observed overall risk pattern. An unconditional SGA classification conceals important differences between clinically distinct subgroups.     

Maternal serum concentrations of perfluoroalkyl substances and birth size in British boys

Per- and polyfluoroalkyl substances (PFAS) have been widely used in commercial and industrial manufacturing processes since the 1950s. Inverse associations between prenatal exposure to PFAS and birth size have been found in populations around the globe. This study examined the association of prenatal maternal serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) and birth size in British boys. The study included 457 mother-son dyads participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Birth weight (g), crown to heel length (cm), and head circumference (cm) were collected at delivery. PFAS were detected in all maternal serum samples during pregnancy (median: 30 weeks gestation (interquartile range: 12–33)). Median concentrations (interquartile range) were 13.8 ng/mL (11.0, 17.7), 3.0 ng/mL (2.3, 3.8), 1.9 ng/mL (1.4, 2.5), and 0.4 ng/mL (0.3, 0.5) for PFOS, PFOA, PFHxS, and PFNA, respectively. In multivariable linear regression models, inverse associations were detected between PFOS (continuous) and birth weight (β = ?8.50 g, 95% CI = ?15.93, ?1.07 g), crown to heel length (β = ?0.04 cm, 95% CI = ?0.08, ?0.01 cm), and head circumference (β = ?0.02 cm, 95% CI = ?0.04, ?0.002 cm). In conclusion, prenatal exposure to high levels of PFOS may be associated with reduced birth size in male infants.     

Maternal coffee drinking in pregnancy and risk of small for gestational age birth

OBJECTIVE: We have analysed the association between coffee drinking before and during the three trimesters of pregnancy and risk of small for gestational age (SGA) birth. METHODS: Cases were 555 women who delivered SGA births (ie <10th percentile according Italian standard). The controls included 1966 women who gave birth at term (>/=37 weeks of gestation) to healthy infants of normal weight. RESULTS: In comparison with nondrinkers, the ORs for SGA birth were 1.3 (95% confidence interval, CI, 0.9-1.9) for consumption of four or more cups of coffee/day before pregnancy, and 1.2 (95% CI 0.8-1.8), 1.2 (95% CI 0.8-1.8) and 0.9 (95% CI 0.6-1.4) for consumption of three or more cups of coffee/day during the first, second and third trimester of pregnancy, respectively. CONCLUSION: These findings were consistent in women who delivered preterm and at term births and were not affected by potential confounding such as smoking.     

Maternal age and parity-associated risks of preterm birth: differences by race/ethnicity

There is a well-known interaction between maternal age and parity in the risk of adverse perinatal outcomes, including preterm birth (PTB), such that young multiparae and older primiparae have greater risks. Yet it is not known whether this interaction varies by race/ethnicity. US birth records for singleton births from 2000 to 2002 were used to examine the incidence of PTB by maternal age and parity within non-Hispanic White, non-Hispanic Black and Hispanic subgroups. PTB was categorised as moderately (32-36 weeks), very (28-31 weeks), or extremely (<28 weeks) preterm. Odds ratios of PTB according to age and parity were calculated in racial/ethnic specific multinomial logistic regression models. Within each race/ethnicity, comparisons were made relative to 25- to 29-year-old primiparae. Young teenagers (<18), particularly multiparae, generally had a higher risk of each degree of PTB among all three racial/ethnic groups. However, Black teenagers did not have a higher risk of extremely PTB. For very and extremely PTB, teenagers had considerably higher risk among Whites than Blacks or Hispanics. Within each racial/ethnic group, older (35+ years) primiparae had similarly higher risk of each category of PTB relative to 25- to 29-year-old primiparae. Older multiparae had higher risk of moderately and very PTB among Black and Hispanic women only. Adjustment for education did not alter these findings. Teenagers and older primiparae are already widely regarded as having greater perinatal risks. This study suggests that, among Black and Hispanic women, older multiparae may also have a higher risk of moderately and very PTB.     

Effects of short interpregnancy intervals on small-for-gestational age and preterm births

We examined the effects of short interpregnancy intervals on small-for-gestational age and preterm births in a biracial population using North Carolina birth certificate data from 1988 to 1994. We defined small-for-gestational age birth as being below the 10th percentile on a race-, sex-, and parity-specific growth curve after a gestation of 37-42 weeks. We defined preterm birth as a gestation of less than 37 weeks. We analyzed birth records from all eligible singleton births to black or white women ages 15-45 years after an interpregnancy interval of 0-3 months (N = 11,451) and a random sample of singleton births after an interval of 4-24 months (N = 23,118). We defined interpregnancy interval exposure categories as 0-3, 4-12, and 13-24 months. The multivariate adjusted odds ratio for small-for-gestational age births after interpregnancy intervals of 0-3 months compared with 13-24-month intervals was 1.6 (95% confidence interval = 1.4-1.8). The odds ratio for preterm birth after interpregnancy intervals of 0-3 months was 1.2 (95% confidence interval = 1.1-1.3). Odds ratios did not vary substantially by race for either outcome.     

Maternal stress and preterm birth

This study examined a comprehensive array of psychosocial factors, including life events, social support, depression, pregnancy-related anxiety, perceived discrimination, and neighborhood safety in relation to preterm birth (<37 weeks) in a prospective cohort study of 1,962 pregnant women in central North Carolina between 1996 and 2000, in which 12% delivered preterm. There was an increased risk of preterm birth among women with high counts of pregnancy-related anxiety (risk ratio (RR) = 2.1, 95% confidence interval (CI): 1.5, 3.0), with life events to which the respondent assigned a negative impact weight (RR = 1.8, 95% CI: 1.2, 2.7), and with a perception of racial discrimination (RR = 1.4, 95% CI: 1.0, 2.0). Different levels of social support or depression were not associated with preterm birth. Preterm birth initiated by labor or ruptured membranes was associated with pregnancy-related anxiety among women assigning a high level of negative impact weights (RR = 3.0, 95% CI: 1.7, 5.3). The association between high levels of pregnancy-related anxiety and preterm birth was reduced when restricted to women without medical comorbidities, but the association was not eliminated. The prospective collection of multiple psychosocial measures on a large population of women indicates that a subset of these factors is associated with preterm birth.     

Maternal pregravid weight, age, and smoking status as risk factors for low birth weight births.

The Illinois Department of Public Health, in cooperation with the Centers for Disease Control (CDC), monitors trends in the prevalence of prenatal risk factors that are major predictors of infant mortality and low birth weight (LBW). Analyzed data from CDC are available to the department annually. During 1988, a total of 26,767 records of Illinois women giving birth were submitted to CDC. These surveillance data support the fact that women older than 30 years who smoke and enter pregnancy underweight are at greatest risk of delivering LBW babies. Overall, 13.9 percent of underweight smokers had LBW infants compared with 8 percent of underweight nonsmokers. Prevalence of LBW among underweight and smoking women older than 34 years was much higher (29.6 percent) than among those between ages 30 and 34 (15.2 percent). The prevalence of LBW decreased as the pregravid weight increased among normal weight smokers (10 percent) and overweight smokers (8.6 percent).     

Associations of prenatal exposure to organophosphate pesticide metabolites with gestational age and birth weight

Background: Prenatal exposure to organophosphate (OP) insecticides, a widely used class of pesticides, may be associated with decreased gestational age and lower birth weight. Single nucleotide polymorphisms in paroxanase (PON1) enzyme genotypes may modify the relationships between OP exposure and perinatal outcomes.Objective: We examined the relationship of prenatal OP insecticide exposure, measured using urinary dialkyl phosphate (DAP) metabolite concentrations, with gestational age and birth weight.Methods: We measured the concentrations of six nonspecific DAP metabolites of OP insecticides in two maternal spot urine samples collected in a prospective birth cohort. We performed multivariable regression to examine associations between the sum of six DAP concentrations (ΣDAP) with gestational age and birth weight. We also examined whether these associations differed according to infant PON1₁₉₂ and PON1_–108 genotypes.Results: Among 306 mother–infant dyads, a 10-fold increase in ΣDAP concentrations was associated with a decrease in covariate-adjusted gestational age [–0.5 weeks; 95% confidence interval (CI): –0.8, –0.1] and birth weight (–151 g; CI: –287, –16); the decrements in birth weight were attenuated after adjusting for gestational age. The relationship between ΣDAP concentrations and gestational age was stronger for white (–0.7 weeks; CI: –1.1, –0.3) than for black (–0.1 weeks; 95% CI: –0.9, 0.6) newborns. In contrast, there was a greater decrease in birth weight with increasing urinary ΣDAP concentrations for black (–188 g; CI: –395, 19) than for white (–118 g; CI: –296, 60) newborns. Decrements in birth weight and gestational age associated with ΣDAP concentrations were greatest among infants with PON1_192QR and PON_–108CT genotypes.Conclusions: Prenatal urinary ΣDAP concentrations were associated with shortened gestation and reduced birth weight in this cohort, but the effects differed by race/ethnicity and PON1_192/108 genotypes.     

Risk factors for small-for-gestational age births among infants in Brazil

OBJECTIVE: To assess the risk factors for small-for-gestational-age (SGA) births. METHODS: All live births occurring in the city of Pelotas, Brazil, between October and December 1993 were identified and mothers interviewed soon after delivery. Birthweight was recorded by the maternity staff. Gestational age was obtained from the mothers' recall of their date of last menstrual period. SGA was defined as a birthweight below the 10th percentile for gestational age and sex, according to the reference developed by Williams. Chi-square test and logistic regression were used in the crude and multivariate analysis, respectively. RESULTS: In all, 1082 births were identified. The prevalence of SGA was 13.1%. Even after adjusting for possible confounding variables, the odds ratio for SGA among those infants whose family income was <1 minimum wage was 8.81 (95% CI, 1.12-69.46) times higher than among those for infants with a family income > or = minimum wage. An antenatal care of low quality was associated with an odds ratio of 3.28 (95% CI, 1.09-9.91) for SGA. Short maternal stature and maternal smoking during pregnancy were also associated with SGA births. CONCLUSIONS: Low socioeconomic status, maternal smoking during pregnancy, maternal height and an antenatal care of low quality are the main risk factors for SGA births.     

Risk of small-for-gestational age is associated with common anti-inflammatory cytokine polymorphisms

BACKGROUND: Anti-inflammatory cytokines play a key role in pregnancy maintenance. Genetic variation in anti-inflammatory cytokines could influence a woman's risk of adverse reproductive outcomes. METHODS: We investigated the relationship of polymorphisms in interleukin 4 (IL4), IL5, IL10, IL13, and transforming growth factor (TGFbeta1) with spontaneous preterm birth and small-for-gestational age (SGA) in a nested case-control study of a prospective pregnancy cohort. Women were recruited between 24 and 29 weeks' gestation at the Wake County and University of North Carolina, Chapel Hill obstetric clinics between February 1996 and June 2000. We inferred haplotypes using the EM algorithm and the Bayesian method, PHASE. Semi-Bayesian hierarchical logistic regression was used to obtain odds ratio (OR) estimates and 95% confidence intervals (CIs) for each polymorphism. RESULTS: African-American mothers who carried the IL4 GCC haplotype had greater risk of spontaneous preterm birth (OR = 2.9; 95% CI = 1.2-7.4). In white mothers, carriers of the "low-producing" IL4 CC and IL10 ATA haplotypes had markedly reduced risk of SGA (for the CC haplotype, 0.2 [0.0-1.2]; for the ATA haplotype, 0.5 [0.3-0.8]), whereas carriers of the "high-producing" IL4(-589)T variant had increased risk of SGA in both African-American and white mothers. CONCLUSIONS: Variants related to decreased anti-inflammatory cytokine production may lower risk of SGA. Furthermore, the same mechanism that protects against SGA might increase risk of spontaneous preterm birth.     

Maternal risk of breast cancer and birth characteristics of offspring by time since birth.

We examined the association between birth characteristics of offspring and the subsequent maternal risk of breast cancer in a population-based cohort of 998,499 women, 13 to 48 years of age at entry. There were 9,495 incident cases of breast cancer during 12.8 million person-years of follow-up among these women. Compared with mothers of singleton infants, mothers having a multiple birth had an increased risk of breast cancer in the first 5 years after a birth (relative risk (RR) = 1.8; 95% confidence interval (CI) = 1.1-2.8). The risk for mothers having a heavy-weighted child (>3.75 kg), as compared with a child of light weight (< or =3 kg), was also slightly increased (RR = 1.2; 95% CI = 0.9-1.5). This latter effect was primarily due to an increased incidence of tumors larger than 2 cm at diagnosis (RR = 1.4; 95% CI = 0.9-1.9). Our findings are compatible with the hypothesis that the hormonal level during pregnancy influences the risk of breast cancer in the early years after delivery.