The maternal Mediterranean dietary pattern is associated with a reduced risk of spina bifida in the offspring

Objective  The objective of this study was to test the hypothesis whether a maternal dietary pattern is associated with the risk of spina bifida (SB) in the offspring.
Design  Case–control study.
Setting  Eight clinic sites in the Netherlands, 1999–2001.
Sample  A total of 50 mothers of children with SB and 81 control mothers.
Methods  Maternal food intakes were obtained by food frequency questionnaires at the standardised study moment of 14 months after the birth of the index child. Principal component factor analysis (PCA) and reduced rank regression (RRR) were used to identify dietary patterns.
Main outcome measures  Maternal biomarkers were used as response measures in the RRR analysis and composed of serum and red blood cell (RBC) folate, serum vitamin B12 and total plasma homocysteine. The strength of the use of the dietary pattern in association with SB risk was estimated by odds ratios and 95% CI with the highest quartiles of the dietary pattern as reference.
Results  A predominantly Mediterranean dietary pattern was identified by both PCA and RRR. Those dietary patterns were highly correlated ( r = 0.51, P < 0.001) and characterised by joint intakes of fruit, vegetables, vegetable oil, alcohol, fish, legumes and cereals and low intakes of potatoes and sweets. We observed a significantly increased risk of SB offspring in mothers with a weak use of the Mediterranean dietary pattern, OR 2.7 (95% CI 1.2–6.1) and OR 3.5 (95% CI 1.5–7.9). The Mediterranean dietary pattern was correlated with higher levels of serum and RBC folate, serum vitamin B12 and lower plasma homocysteine.
Conclusion  The Mediterranean dietary pattern seems to be associated with reduction in the risk of offspring being affected by SB.     

Nutrient composition of hindmilk produced by mothers of very low birth weight infants born at less than 28 weeks' gestation.

The objectives of this study were to describe and compare retinol, alpha-tocopherol and gamma-tocopherol, fat, energy, and nitrogen concentrations between the foremilk and hindmilk fractions of 24-hour milk collected by 24 mothers of very preterm (< 28 weeks' gestation) infants and to relate milk vitamins A and E content to maternal vitamin intake. Concentrations of retinol were significantly higher in hindmilk than in foremilk (1.6-fold), as were concentrations of alpha-tocopherol (1.6-fold), gamma-tocopherol (1.5-fold), fat (1.7-fold), energy (1.3-fold), and nitrogen (1.05-fold). Retinol, alpha-tocopherol, and gamma-tocopherol were positively related (P < .05) to milk fat and energy but not to maternal intake. Estimates of vitamins A and E intakes of infants fed hindmilk with added human milk fortifier surpassed current recommended upper level of intakes. The higher fat-soluble vitamin content of hindmilk produced by mothers of very low birth weight infants needs to be considered in the design and recommendations for use of human milk fortifier.     

Relationship between pregnancy outcomes and maternal vitamin D and calcium intake: A cross-sectional study

Poor maternal vitamin D status affects fetal and infant skeletal growth. The aim of the present study was to determine the association between newborn outcomes and maternal calcium and vitamin D intakes. Four hundred and forty-nine pregnant women, healthy at the point of delivery, and their newborns were enrolled in the study, which was performed in three university hospitals in Tehran in March 2004. Maternal anthropometric data and energy, protein, calcium and vitamin D intakes were collected, and newborn outcomes (weight, length, head circumference and 1-min Apgar score) were determined. Almost two-thirds of the mothers (64.3%) took no supplements during pregnancy. Only one-third of the mothers (33.8%) had adequate intakes of calcium and vitamin D (from supplements and foods) compared with the Recommended Dietary Allowances. Mean length at birth and 1-min Apgar score were higher in newborns whose mothers had adequate calcium and vitamin D intake than in newborns whose mothers had inadequate intake (p = 0.03 and p = 0.04, respectively). Significant correlations were found between adequate maternal calcium and vitamin D intake and both appropriate birth weight and 1-min Apgar score of newborns and weight gain of mothers during pregnancy. Informing mothers of the critical importance of consuming adequate amounts of calcium and vitamin D seems necessary.     

Periconceptional intake of folic acid and food folate and risks of preterm delivery

We investigated multiple sources of folate and folic acid to determine whether their periconceptional intakes were associated with preterm delivery. Studied were controls from the National Birth Defects Prevention Study delivered September 1998 to December 2005. Telephone interviews were conducted with 5952 (68% of eligible) mothers. Women were queried about intake of vitamin supplements in the 12 weeks before conception through delivery. A version of the Nurse's Health Study food frequency questionnaire was used to assess food sources. Eight percent of infants ( N?=?487) were preterm (<37 weeks). Compared with women who began intake of supplements with folic acid before pregnancy, those who began any time during pregnancy had an ~20% lowered risk of preterm delivery. Lower dietary intakes showed a modest increased risk of preterm delivery: odds ratios were 1.44 (1.01 to 2.04) for lowest quartile intake of folate and 1.27 (0.95 to 1.69) for lowest quartile intake of folic acid compared with the highest. Findings suggest some evidence that folates influenced risks; however, an interpretation of results was also consistent with no association between intake of folates and preterm delivery.     

Relationship between pregnancy outcomes and maternal vitamin D and calcium intake: A cross-sectional study.

Poor maternal vitamin D status affects fetal and infant skeletal growth. The aim of the present study was to determine the association between newborn outcomes and maternal calcium and vitamin D intakes. Four hundred and forty-nine pregnant women, healthy at the point of delivery, and their newborns were enrolled in the study, which was performed in three university hospitals in Tehran in March 2004. Maternal anthropometric data and energy, protein, calcium and vitamin D intakes were collected, and newborn outcomes (weight, length, head circumference and 1-min Apgar score) were determined. Almost two-thirds of the mothers (64.3%) took no supplements during pregnancy. Only one-third of the mothers (33.8%) had adequate intakes of calcium and vitamin D (from supplements and foods) compared with the Recommended Dietary Allowances. Mean length at birth and 1-min Apgar score were higher in newborns whose mothers had adequate calcium and vitamin D intake than in newborns whose mothers had inadequate intake (p = 0.03 and p = 0.04, respectively). Significant correlations were found between adequate maternal calcium and vitamin D intake and both appropriate birth weight and 1-min Apgar score of newborns and weight gain of mothers during pregnancy. Informing mothers of the critical importance of consuming adequate amounts of calcium and vitamin D seems necessary.     

Folic acid use in pregnancy and embryo selection

Objective  Folic acid supplement use is recommended in pregnancy to reduce the risk of neural tube defect but concerns have been raised that increasing folic acid intake may select for embryos with genotypes that increase disease risk in the offspring. Our aim was to test for this effect.
Design  Observational prospective cohort study.
Setting  Aberdeen Maternity Hospital.
Population or Sample  Women born before the introduction of folic acid advice (1970–80) and carrying singleton pregnancies ( n = 1234) and their offspring ( n = 1083) born after (2001–03).
Methods  We measured the genotype ( MTHFR C677T and A1298C, MTR A2756G, MTRR A66G and TCN G776C ) of mothers and their offspring, maternal supplement intake, intake of folate and vitamin B12 from natural foods and maternal blood folate and B12 status at 19 weeks of gestation.
Main outcome measures  B vitamin related genotype of the offspring.
Results  There were no significant differences in any of the five genotype frequencies between mothers and their babies. There was no deviation from Hardy–Weinberg equilibrium in either generation and no change in the frequency of doubly homozygous
MTHFR variants (677 TT/1298 CC). The genotype of the offspring was not related to maternal periconceptual supplement use, folate intake from foods or plasma and red cell folate measured at 19 weeks of gestation.
Conclusions  We found no evidence to support the concern that folic acid fortification or supplement use in pregnancy results in selection of deleterious genotypes.     

World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries

Objective  To determine if vitamin C and E supplementation in high-risk pregnant women with low nutritional status reduces pre-eclampsia.
Design  Multicentred, randomised, controlled, double-blinded trial.
Setting  Antenatal care clinics and Hospitals in four countries.
Population  Pregnant women between 14 and 22 weeks' gestation.
Method  Randomised women received 1000 mg vitamin C and 400 iu of vitamin E or placebo daily until delivery.
Main outcome measures  Pre-eclampsia, low birthweight, small for gestational age and perinatal death.
Results  Six hundred and eighty-seven women were randomised to the vitamin group and 678 to the placebo group. Groups had similar gestational ages (18.1; SD 2.4 weeks), socio-economic, clinical and demographical characteristics and blood pressure at trial entry. Risk factors for eligibility were similar, except for multiple pregnancies: placebo group (14.7%), vitamins group (11.8%). Previous pre-eclampsia, or its complications, was the most common risk factor at entry (vitamins 41.6%, placebo 41.3%). Treatment compliance was 87% in the two groups and loss to follow-up was low (vitamins 2.0%, placebo 1.3%). Supplementation was not associated with a reduction of pre-eclampsia (RR: 1.0; 95% CI: 0.9–1.3), eclampsia (RR: 1.5; 95% CI: 0.3–8.9), gestational hypertension (RR: 1.2; 95% CI: 0.9–1.7), nor any other maternal outcome. Low birthweight (RR: 0.9; 95% CI: 0.8–1.1), small for gestational age (RR: 0.9; 95% CI: 0.8–1.1) and perinatal deaths (RR: 0.8; 95% CI: 0.6–1.2) were also unaffected.
Conclusion  Vitamins C and E at the doses used did not prevent pre-eclampsia in these high-risk women.     

Vitamin C and the risk of gestational diabetes mellitus: a case-control study

OBJECTIVE: To examine whether low maternal dietary intake of vitamin C and low maternal plasma ascorbic acid (AA) concentrations are associated with an increased risk of gestational diabetes mellitus (GDM). METHODS: Cases were 67 women with GDM meeting National Diabetes Data Group criteria. Controls were 260 women without such a diagnosis. Maternal dietary vitamin C consumption during the periconceptional period and during pregnancy was assessed using a 121-item, semiquantitative food frequency questionnaire. Maternal plasma AA concentrations were determined using automated enzymatic procedures on specimens collected during the intrapartum period. RESULTS: Mean maternal daily consumption of vitamin C and plasma AA concentrations were 10% and 31% lower, respectively, among GDM cases as compared with controls (130.7 +/- 10.2 vs. 145 +/- 4.9 mg/d, P = .190; 36 +/- 2.0 vs. 53 +/- 1.0 micromol/L, P <.001). After controlling for maternal age, race, prepregnancy adiposity, family history of type 2 diabetes, energy intake and income, women reporting low daily vitamin C intake (< 70 mg/d), as compared with the other women, experienced a 3.7-fold increased risk of GDM (odds ratio [OR] = 3.7, 95% confidence interval [CI] 1.7-8.2). There was a linear relation in risk of GDM with decreasing concentrations of plasma AA (P for linear trend <.001). After adjusting for confounders, women in the lowest quartile (< 42.6 micromol/L), as compared with women in the highest quartile (> 63.3 micromol/L), experienced > 12-fold increased risk of GDM (OR = 12.8, 95% CI 3.5-46.2). CONCLUSION: Low maternal dietary vitamin C intake and low plasma AA concentrations are associated with an increased risk of GDM. Large, prospective, cohort studies are needed to further evaluate the potential beneficial role of vitamin C and other antioxidants in the prevention of impaired glucose tolerance in pregnancy.     

Plasma vitamin A in mothers of children with orofacial clefts

OBJECTIVES: The contribution and exact role of exogenous factors, such as medications and drugs during pregnancy, maternal nutrition, in the etiology of orofacial clefts is not established. Vitamin A is essential for embryogenesis, both the lack and excess of retinol result in congenital malformations. DESIGN: This study was aimed to establish vitamin A status in Polish mothers of children with isolated orofacial clefts. MATERIAL AND METHODS: 34 mothers of children with isolated cleft lip (CL), 83 mothers of children with cleft lip and palate (CLP), 42 mothers of children with isolated cleft palate (CP) were studied. The control group consisted of 67 women who gave birth to healthy children. All participants were healthy women without symptoms of malabsorption. Plasma retinol levels were determined by high-performance liquid chromatography. RESULTS: There were no differences in mean plasma vitamin A levels between CL--2.09 +/- 0.61 mumol/l, CLP--2.21 +/- 0.52 mumol/l, CP--2.15 +/- 0.62 mumol/l and control--2.08 +/- 0.52 mumol/l. None of participants had vitamin A deficiency (concentration of retinol < 0.8 mumol/l). Among women, who were not supplemented with retinol containing vitamins during 3 months prior the study, 10.6% of mothers of children with orofacial clefts (n = 132) and only 5.8% of controls (n = 52) had levels of retinol above upper norm for women of childbearing age (N < 2.8 mumol/l). CONCLUSION: Periconceptional multivitamin supplementation has been reported to decrease the risk of orofacial clefts in offspring, but high intake of preformed vitamin A (retinol) might be undesirable.     

Dietary intake of vitamin C and vitamin E and the development of hypertensive disorders of pregnancy

OBJECTIVES: To explore the relationship, if any, between dietary intake of the antioxidant vitamins C and E, and the development of pre-eclampsia and gestational hypertension. STUDY DESIGN: A prospective cohort study of pregnant women attending the antenatal clinic of the Women's and Children's Hospital in Adelaide, Australia, was carried out between April and July 2001. Women completed a semi-quantitative 116-item food frequency questionnaire (FFQ). Women's medical records were viewed after birth to collect data on pregnancy outcomes. Relationships were explored through cross-tabulations, chi-square analysis, and adjustments were made for potential confounders using binary logistic regression. RESULTS: A total of 299 women completed the FFQ. Median intake of vitamin C was 188 mg and for vitamin E was 6.74 mg. There was no relationship between the intake of vitamin C and hypertensive disorders of pregnancy. For vitamin E, being in the lowest quartile of intake, was associated with an increased risk of hypertensive disorders (RR 1.75, 95% CI 1.11-2.75, P = 0.02). This relationship was confirmed after adjusting for the confounding factors of maternal age and parity. CONCLUSIONS: Little support was found for a relationship between dietary intake of vitamin C and the development of hypertensive disorders of pregnancy. Low vitamin E intake was associated with a significant increase in the risk of hypertensive disorders of pregnancy, even after adjustments were made for confounding factors. Further research is required to investigate whether supplementation above dietary intake of antioxidant vitamins influences the risk of hypertensive disorders of pregnancy.     

Diet in late pregnancy and glucose-insulin metabolism of the offspring 40 years later

Objective To determine how diets of women in pregnancy influence the glucose-insulin metabolism of their offspring in adult life.
Design A follow up study of men and women born during 1948–1954 whose mothers had taken part in a survey of diet in late pregnancy.
Setting Aberdeen, Scotland.
Population One hundred and sixty-eight men and women born in the Aberdeen Maternity Hospital.
Main outcome measure Plasma glucose and insulin concentrations, fasting and after a standard oral glucose challenge.
Results The offspring of women who had high intakes of fat and protein in late pregnancy had a reduced plasma insulin increment between fasting and 30 min with a 7.0% decrease in increment (   P = 0.007  ) per 10 g increase in protein intake and a 4.9% decrease (   P = 0.002  ) per 10 g increase in fat intake. This was independent of the mother's body mass index or weight gain in pregnancy. A low maternal body mass index in early or late pregnancy was associated with a raised fasting plasma insulin concentration with a decrease of 2.4% (   P = 0.05  ) per 1 kg/m ² increase of maternal body mass.
Conclusion High intakes of protein and fat during pregnancy may impair development of the fetal pancreatic beta cells and lead to insulin deficiency in the offspring. The offspring of thin mothers tend to be insulin resistant.     

Association between antidepressant drug use during pregnancy and child healthcare utilisation

Objective  To evaluate healthcare utilisation by children who were exposed to antidepressant drug use during pregnancy and those whose mothers stopped using antidepressants before pregnancy compared with a control group.
Design  Cohort study.
Setting  Health insurance records in the Netherlands.
Population  A total of 38 602 children born between 2000 and 2005.
Methods  Survey of child healthcare utilisation in relation to gestational antidepressant use.
Main outcome measure  Healthcare utilisation rates during the first year of life, with special emphasis to medical care related to cardiac disease.
Results  Children of mothers who used antidepressants during pregnancy showed increased healthcare use during the first year of life, independent of the mother's healthcare use. The relative risk of more than two visits to general practitioners was 1.5 (95% confidence interval, CI: 1.3–1.8) in the continuous antidepressant users group and 1.3 (95% CI: 1.2–1.5) in the group of children whose mothers stopped taking medication. In both study groups there was a trend towards more drug use for infections and inflammation compared with the control group. Children continuously exposed to antidepressants had an increased risk of cardiac interventions such as cardiovascular surgery or heart catheterisation, relative risk of 5.6 (95% CI: 1.8–17.4). The risk of physiotherapy was twice as high in the antidepressant group compared with the control group (relative risk 2.0; 95% CI: 1.5–2.6).
Conclusion  Antidepressant use during pregnancy is associated with increased child healthcare utilisation and increased risk of major cardiac interventions in early childhood.     

Fetal macrosomia and pregnancy outcomes

Background:  Pregnancies with a macrosomic fetus comprise a subgroup of high-risk pregnancies. There is uncertainty in the clinical management and outcomes of such pregnancies.
Aim:  We sought to examine clinical management and maternal and fetal outcomes in pregnancies with macrosomic infants at Royal Brisbane and Women's Hospital (RBWH).
Methods:  Data from 276 macrosomic births (weighing ≥ 4500 g) and 294 controls (weighing 3250–3750 g) delivered during 2002–2004 at RBWH were collected from the hospital database. Univariate and logistic regression analyses were performed for maternal risk factors and maternal and neonatal outcomes that were associated with fetal macrosomia.
Results:  Macrosomia was more than two times likely in women with body mass index (BMI) of  > 30 kg/m² (odds ratio (OR) 2.41, 95% confidence interval (CI) 1.26–4.61) and in male infant sex (OR 2.05, 95% CI 1.35–3.12), and four times more likely in gestation of > 40 weeks (OR 3.93, 95% CI 1.99–7.74). Maternal smoking reduced the risk of fetal macrosomia (OR 0.27, 95% CI 0.14–0.51).
Macrosomia was associated with nearly two times higher risk of emergency caesarean section (OR 1.75, 95% CI 1.02–2.97) and maternal hospital stay of > 3 days (OR 1.66, 95% CI 1.11–2.50), and four times higher risk of shoulder dystocia (OR 4.08, 95% CI 1.62–10.29). Macrosomic infants were twice as likely to have resuscitation (OR 2.21, 95% CI 1.46–3.34) and intensive care nursery admission (OR 1.89, 95% CI 1.03–3.46).
Conclusion:  Macrosomia was associated with an increased risk of adverse maternal and neonatal health outcomes. Optimal management strategies of macrosomic pregnancies need evaluation.     

Teenage pregnancies and risk of late fetal death and infant mortality

Objective To estimate the effect of low maternal age on late fetal death and infant mortality and to estimate the extent of any increase in infant mortality attributable to higher rates of preterm birth among teenagers.
Design Population-based cohort study.
Setting Births recorded in the nationwide Swedish Medical Birth Registry.
Population All single births to nulliparous women aged 13–24 years (   n = 320  ,174) during 1973–1989.
Methods Using information recorded in the medical birth registry, linked to a national education register, the effect of low maternal age on adverse outcomes was estimated using logistic regression analysis.
Main outcome measures Late fetal death, neonatal and postneonatal mortality and preterm birth.
Results Compared with mothers aged 2CL24 years, adjusted risks of neonatal and postneonatal mortality were significantly increased among mothers aged 13–15 years (odds ratios = 2.7 and 2.6, respectively) and among those aged 16–17 years (odds ratios = 1.4 and 2.0, respectively), while mothers aged 18–19 years had a significant increase in risk of postneonatal mortality only (odds ratio = 1.4). Rates of very preterm birth (≤ 32 weeks), according to maternal age, were: 13–15 years, 5.9%; 16–17 years, 2.5%; 18–19 years, 1.7%; and 20–24 years, 1.1%. The high rates of very preterm birth among young teenagers almost entirely explained the increased risk of neonatal mortality in this group.
Conclusions The increased risks of neonatal and postneonatal mortality among young teenagers may be related to biological immaturity. The increase in risk of neonatal mortality is largely explained by increased rates of very preterm birth.     

Vitamin A and risk of cervical cancer: a meta-analysis

Objective

To conduct a systematic review with meta-analysis of studies assessing the association of vitamin A (retinol, carotene and other carotenoids) intake or blood (serum or plasma) levels of vitamin A (retinol and carotene) with risk of cervical cancer.

Methods

We evaluated the studies published in English and Chinese on diet or blood vitamin A for the risk of cervical cancer. We also reviewed reference lists from retrieved articles. Meta-analysis was applied to calculate the combined effect values and their 95% confidence intervals. The risk of bias was assessed by the Egger regression asymmetry test.

Results

As many as 11 articles on dietary vitamin A and 4 articles on blood vitamin A were selected according to the eligibility criteria and were included in the meta-analysis, for a total of 12,136 participants. The pooled odds ratios (ORs) of cervical cancer were 0.59 (95% CI, 0.49-0.72) for total vitamin A intake and 0.60 (95% CI, 0.41-0.89) for blood vitamin A levels. The combined ORs of cervical cancer were 0.80 (95% CI, 0.64-1.00), 0.51 (95% CI, 0.35-0.73) and 0.60 (95% CI, 0.43-0.84) for retinol, carotene and other carotenoid intake, and 1.14 (95% CI, 0.83-1.56) and 0.48 (95% CI, 0.30-0.77) for blood retinol and carotene.

Conclusions

Vitamin A intake and blood vitamin A levels were inversely associated with the risk of cervical cancer in this meta-analysis.     

Estimates of maternal mortality by the sisterhood method in rural nothern Tanzania: a household sample and an antenatal clinic sample

Objective To estimate maternal mortality in two samples of a population in northern Tanzania.
Setting Rural communities and antenatal clinics, Mbulu and Hanang districts, Arusha region, Tanzania.
Population From a household survey 2043 men and women aged 15–60, and from an antenatal clinic survey 4172 women aged 15–59.
Method The indirect sisterhood method.
Main outcome measures The risk of maternal deaths per 100,000 live births (maternal mortality ratio), and the lifetime risk of a maternal death.
Results The risk of a maternal death per 100,000 live births was 362 (95% CI 269–456) and 444 (95% CI 371–517) for the household and antenatal clinic surveys, respectively. The lifetime risk of maternal death was 1 in 38 and 1 in 31, respectively, for the two surveys. A significantly lower risk of maternal death was observed for the respondents attending antenatal clinics closer to the hospital than for those attending clinics further away: 325 (95% CI 237–413) compared with 561 (95% CI 446–677) per 100,000 live births. Lifetime risk of maternal death was 1 in 42 and 1 in 25, respectively.
Conclusions The risk of maternal death per 100,000 live births in this area were comparatively high, but in our survey substantially lower than in previous surveys in Tanzania. Increasing distance from the antenatal clinics to the hospital was associated with higher maternal mortality. There was no significant difference between results based on household and antenatal clinic data, suggesting that accessible health facility data using the sisterhood method may provide a basis for local assessment of maternal mortality in developing countries.     

Diet in pregnancy and the offspring's blood pressure 40 years later

Objective To determine how diet of the mother in pregnancy influences the blood pressure of the offspring in adult life.
Design A follow up study of men and women born during 1948–1954 whose mothers had taken part in a survey of diet in late pregnancy.
Setting Aberdeen, Scotland.
Population Two hundred and fifty-three men and women born in Aberdeen Maternity Hospital.
Main outcome measure Systolic and diastolic blood pressure.
Results The relations between the diet of mothers and their offsprings' blood pressure were complex. When the mothers' intake of animal protein was less than 50 g daily, a higher carbohydrate intake was associated with a higher blood pressure in the offspring (a 100 g increase in carbohydrate being associated with a 3 mmHg increase in systolic pressure (   P = 0.02  )). At daily animal protein intakes above 50 g, lower Carbohydrate intake was associated with higher blood pressure (a 100 g decrease in carbohydrate being associated with an 11 mmHg rise in systolic blood pressure (   P = 0.004  )). These increases in blood pressure were associated with decreased placental size.
Conclusion Mothers' intakes of animal protein and carbohydrate in late pregnancy may influence their offsprings' adult blood pressure. This may be mediated through effects on placental growth.     

The incidence of preterm deliveries decreases in Finland

Objective  We examined the trends and risk factors of preterm delivery.
Design  Register-based retrospective cohort study from Finland.
Setting  National Medical Birth Register data during 1987–2005.
Population  The study population consisted of 1 137 515 deliveries, of which 59 025 were preterm (5.2%).
Methods  We calculated the population attributable risks for using the risk factor prevalence rates in the population. We further calculated odds ratios with 95% CI by multivariate logistic regression to adjust for confounders.
Main outcome measures  Preterm delivery rate subclassified into moderately preterm (32–36 weeks), very preterm (28–31 weeks) and extremely preterm (less than 28 weeks).
Results  Preterm delivery rates increased from 5.1% in the late 1980s to 5.4% in the late 1990s but then decreased to 5.2% for 2001–05. The proportion of extremely preterm deliveries decreased substantially by 12% ( P < 0.01). The greatest risk factors were multiplicity (OR 13.72, 95% CI 13.26–14.19), followed by elective delivery (OR 1.86, 95% CI 1.82–1.89), primiparity (OR 1.47, 95% CI 1.45–1.50), in vitro fertilisation treatment (OR 1.39, 95% CI 1.31–1.47), maternal smoking (OR 1.31, 95% CI 1.29–1.34) and advanced maternal age (OR 1.02, 95% CI 1.02–1.03 for each additional year of age). Prematurity rates decreased by 1.8% after adjusting for risk variables.
Conclusions  The rate of preterm delivery has not increased from 1987 to 2005 in Finland, while the risk for extremely preterm delivery has decreased. This finding is in contrast with recent trends in other countries.     

Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease

OBJECTIVE: To investigate the inter-relation between mother and infant homocysteine, folate and vitamin B12 status and the risk of a child with congenital heart disease (CHD). DESIGN: Case-control study. SETTING: Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. POPULATION: Participants were 149 case-mothers and their children with CHD (n = 151) and 183 control-mothers with their children (n = 175). METHODS: Approximately 17 months after the index-pregnancy maternal fasting, children's random venous blood samples were drawn to measure plasma total homocysteine, serum and red blood cell (RBC) folate, and serum vitamin B12 concentrations. Data were compared between cases and controls using the Mann-Whitney U test. The biochemical parameters were dichotomised according to the cutoff value of the 10th percentile of vitamin concentrations and the 90th percentile of homocysteine concentrations based on control data. Risk estimates for the association between CHD and the biochemical parameters were estimated in a logistic regression model. MAIN OUTCOME MEASURES: Medians (minimum-maximum) and odds ratios (OR) (95% confidence intervals [CI]). RESULTS: The OR (95% CI) of having a child with CHD was 2.9 (1.4-6.0) for maternal hyperhomocysteinaemia (>14.3 micromol/l). This finding is substantiated by a significant concentration-dependent risk (Ptrend = 0.004). Hyperhomocysteinaemic case-mothers showed significantly lower serum folate and vitamin B12 concentrations than normohomocysteinaemic case-mothers. Serum and RBC folate concentrations were significantly higher in case-children than that in control-children. CONCLUSIONS: Maternal hyperhomocysteinaemia is associated with an increased risk of CHD, partially due to low folate and vitamin B12 status. The folate status of children warrants further investigation.     

Antiepileptic drug use, folic acid supplementation, and congenital abnormalities: a population-based case-control study

Objective  To investigate whether folic acid supplementation in early pregnancy modifies the association between the prevalence of congenital abnormalities in the offspring and maternal use of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and primidone (PRI).
Design  A population-based case–control study.
Setting  The Hungarian Case–Control Surveillance of Congenital Abnormalities (HCCSCA) (1980–1996) and its information on children from the Hungarian Congenital Abnormality Registry and the Hungarian National Birth Registry.
Population  Children with congenital abnormalities (cases; n = 20 792, of whom 148 had been exposed to antiepileptic drugs [AEDs]) and unaffected children (controls; n = 38 151, of whom 184 had been exposed to AEDs).
Methods  Information on drug exposure and background variables for the mothers were collected from antenatal logbooks, discharge summaries, and structured questionnaires completed by the mothers at the time of HCCSCA registration.
Main outcome measures  Congenital abnormalities detected at termination of pregnancy, at birth or until 3 months of age according to CBZ, PB, PHT, or PRI exposure at 5–12 weeks from first day of the last menstrual period (LMP), stratified by folic acid supplementation.
Results  Compared with children unexposed to AEDs and folic acid, the odds ratio of congenital abnormalities was 1.47 (95% CI 1.13–1.90) in children exposed to AEDs without folic acid supplementation and 1.27 (95% CI 0.85–1.89) for children exposed to AEDs with folic acid supplementation.
Conclusion  The results indicate that the risk of congenital abnormalities in children exposed in utero to CBZ, PB, PHT, and PRI is reduced but not eliminated by folic acid supplementation at 5–12 weeks from LMP. The statistical precision in our study is limited due to rarity of the exposures, and further studies are needed.