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1.  Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands 
BMJ : British Medical Journal  2004;328(7445):915.
Objective To investigate maternal, perinatal, and neonatal outcomes of pregnancies in women with type 1 diabetes in the Netherlands.
Design Nationwide prospective cohort study.
Setting All 118 hospitals in the Netherlands.
Participants 323 women with type 1 diabetes who became pregnant between 1 April 1999 and 1 April 2000.
Main outcome measures Maternal, perinatal, and neonatal outcomes of pregnancy.
Results 84% (n = 271) of the pregnancies were planned. Glycaemic control early in pregnancy was good in most women (HbA1c ≤ 7.0% in 75% (n = 212) of the population), and folic acid supplementation was adequate in 70% (n = 226). 314 pregnancies that went beyond 24 weeks' gestation resulted in 324 infants. The rates of pre-eclampsia (40; 12.7%), preterm delivery (101; 32.2%), caesarean section (139; 44.3%), maternal mortality (2; 0.6%), congenital malformations (29; 8.8%), perinatal mortality (9; 2.8%), and macrosomia (146; 45.1%) were considerably higher than in the general population. Neonatal morbidity (one or more complications) was extremely high (260; 80.2%). The incidence of major congenital malformations was significantly lower in planned pregnancies than in unplanned pregnancies (4.2% (n = 11) v 12.2% (n = 6); relative risk 0.34, 95% confidence interval 0.13 to 0.88).
Conclusion Despite a high frequency of planned pregnancies, resulting in overall good glycaemic control (early) in pregnancy and a high rate of adequate use of folic acid, maternal and perinatal complications were still increased in women with type 1 diabetes. Neonatal morbidity, especially hypoglycaemia, was also extremely high. Near optimal maternal glycaemic control (HbA1c ≤ 7.0%) apparently is not good enough.
doi:10.1136/bmj.38043.583160.EE
PMCID: PMC390158  PMID: 15066886
2.  Effect of interpregnancy interval on outcomes of pregnancy after miscarriage: retrospective analysis of hospital episode statistics in Scotland 
Objective To determine the optimum interpregnancy interval after miscarriage in a first recorded pregnancy.
Design Population based retrospective cohort study.
Setting Scottish hospitals between 1981 and 2000.
Participants 30 937 women who had a miscarriage in their first recorded pregnancy and subsequently became pregnant.
Main outcome measures The primary end point was miscarriage, live birth, termination, stillbirth, or ectopic pregnancy in the second pregnancy. Secondary outcomes were rates of caesarean section and preterm delivery, low birthweight infants, pre-eclampsia, placenta praevia, placental abruption, and induced labour in the second pregnancy.
Results Compared with women with an interpregnancy interval of 6-12 months, those who conceived again within six months were less likely to have another miscarriage (adjusted odds ratio 0.66, 95% confidence interval 0.57 to 0.77), termination (0.43, 0.33 to 0.57), or ectopic pregnancy (0.48, 0.34 to 0.69). Women with an interpregnancy interval of more than 24 months were more likely to have an ectopic second pregnancy (1.97, 1.42 to 2.72) or termination (2.40, 1.91 to 3.01). Compared with women with an interpregnancy interval of 6-12 months, women who conceived again within six months and went on to have a live birth in the second pregnancy were less likely to have a caesarean section (0.90, 0.83 to 0.98), preterm delivery (0.89, 0.81 to 0.98), or infant of low birth weight (0.84, 0.71 to 0.89) but were more likely to have an induced labour (1.08, 1.02 to 1.23).
Conclusions Women who conceive within six months of an initial miscarriage have the best reproductive outcomes and lowest complication rates in a subsequent pregnancy.
doi:10.1136/bmj.c3967
PMCID: PMC2917004  PMID: 20688842
3.  Sources and Determinants of Vitamin D Intake in Danish Pregnant Women 
Nutrients  2012;4(4):259-272.
Vitamin D deficiency during pregnancy has been associated with the development of several adverse health outcomes, e.g., pre-eclampsia, gestational diabetes mellitus, preterm delivery, low birth weight, birth length, and bone mineral content. The aims of the present study were to estimate the intake and sources of vitamin D in Danish pregnant women and to examine potential determinants of vitamin D intake of the recommended level (10 µg per day). In 68,447 Danish pregnant women the mean ± SD for vitamin D intake was 9.23 ± 5.60 µg per day (diet: 3.56 ± 2.05 µg per day, supplements: 5.67 ± 5.20 µg per day). 67.6% of the women reported use of vitamin D supplements but only 36.9% reported use of vitamin D supplements of at least 10 µg. Supplements were the primary source of vitamin D for the two higher quartiles of total vitamin D intake, with diet being the primary source for the two lower quartiles. Determinants of sufficient total vitamin D intake were: high maternal age, nulliparity, non-smoking, and filling out of the Food Frequency Questionnaire (FFQ) during summer or fall. We propose that clinicians encourage vitamin D supplementation among pregnant women, with special focus on vulnerable groups such as the young, smokers and multiparous women, in order to improve maternal and fetal health both during and after pregnancy.
doi:10.3390/nu4040259
PMCID: PMC3347007  PMID: 22606369
vitamin D; pregnancy; sources; diet; supplements; determinants; socio-demography; gestation; lifestyle
4.  Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: double blind randomised community trial 
BMJ : British Medical Journal  2003;326(7389):571.
Objective
To assess the impact on birth size and risk of low birth weight of alternative combinations of micronutrients given to pregnant women.
Design
Double blind cluster randomised controlled trial.
Setting
Rural community in south eastern Nepal.
Participants
4926 pregnant women and 4130 live born infants.
Interventions
426 communities were randomised to five regimens in which pregnant women received daily supplements of folic acid, folic acid-iron, folic acid-iron-zinc, or multiple micronutrients all given with vitamin A, or vitamin A alone (control).
Main outcome measures
Birth weight, length, and head and chest circumference assessed within 72 hours of birth. Low birth weight was defined <2500 g.
Results
Supplementation with maternal folic acid alone had no effect on birth size. Folic acid-iron increased mean birth weight by 37 g (95% confidence interval −16 g to 90 g) and reduced the percentage of low birthweight babies (<2500 g) from 43% to 34% (16%; relative risk=0.84, 0.72 to 0.99). Folic acid-iron-zinc had no effect on birth size compared with controls. Multiple micronutrient supplementation increased birth weight by 64 g (12 g to 115 g) and reduced the percentage of low birthweight babies by 14% (0.86, 0.74 to 0.99). None of the supplement combinations reduced the incidence of preterm births. Folic acid-iron and multiple micronutrients increased head and chest circumference of babies, but not length.
Conclusions
Antenatal folic acid-iron supplements modestly reduce the risk of low birth weight. Multiple micronutrients confer no additional benefit over folic acid-iron in reducing this risk.
What is already known on this topicDeficiencies in micronutrients are common in women in developing countries and have been associated with low birth weight and preterm deliveryWhat this study addsIn rural Nepal maternal supplementation with folic acid-iron reduced the incidence of low birth weight by 16%A multiple micronutrient supplement of 14 micronutrients, including folic acid, iron, and zinc, reduced low birth weight by 14%, thus conferring no advantage over folic acid-iron
PMCID: PMC151518  PMID: 12637400
5.  Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review 
BMJ : British Medical Journal  2001;322(7282):329-333.
Objective
To assess the effectiveness and safety of antiplatelet drugs for prevention of pre-eclampsia and its consequences.
Design
Systematic review.
Data sources
Register of trials maintained by Cochrane Pregnancy and Childbirth Group, Cochrane Controlled Trials Register, and Embase.
Included studies
Randomised trials involving women at risk of pre-eclampsia, and its complications, allocated to antiplatelet drug(s) versus placebo or no antiplatelet drug.
Main outcomes measures
Pre-eclampsia, preterm birth, fetal or neonatal death, and small for gestational age baby. Studies were assessed for quality of concealment of allocation and losses to follow up.
Results
39 trials (30 563 women) were included, and 45 trials (>3000 women) excluded. Use of antiplatelet drugs was associated with a 15% reduction in the risk of pre-eclampsia (32 trials, 29 331 women; relative risk 0.85, 95% confidence interval 0.78 to 0.92; number needed to treat 100, 59 to 167). There was also an 8% reduction in the risk of preterm birth (23 trials, 28 268 women; 0.92, 0.88 to 0.97; 72, 44 to 200), and a 14% reduction in the risk of fetal or neonatal death (30 trials, 30 093 women; 0.86, 0.75 to 0.98; 250, 125 to >10 000) for women allocated antiplatelet drugs. Small for gestational age babies were reported in 25 trials (20 349 women), with no overall difference between the groups (relative risk 0.92, 0.84 to 1.01). There were no significant differences in other measures of outcome.
Conclusions
Antiplatelet drugs, largely low dose aspirin, have small to moderate benefits when used for prevention of pre-eclampsia.
PMCID: PMC26574  PMID: 11159655
6.  Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis 
Objective To estimate the contributions of biological aging, historical trends, and birth cohort effects on trends in pre-eclampsia in the United States.
Design Population based retrospective study.
Setting National hospital discharge survey datasets, 1980-2010, United States.
Participants 120 million women admitted to hospital for delivery.
Main outcome measures Temporal changes in rates of mild and severe pre-eclampsia in relation to maternal age, year of delivery, and birth cohorts. Poisson regression as well as multilevel age-period-cohort models with adjustment for obesity and smoking were incorporated.
Results The rate of pre-eclampsia was 3.4%. The age-period-cohort analysis showed a strong age effect, with women at the extremes of maternal age having the greatest risk of pre-eclampsia. In comparison with women delivering in 1980, those delivering in 2003 were at 6.7-fold (95% confidence interval 5.6-fold to 8.0-fold) increased risk of severe pre-eclampsia. Period effects declined after 2003. Trends for severe pre-eclampsia also showed a modest birth cohort effect, with women born in the 1970s at increased risk. Compared with women born in 1955, the risk ratio for women born in 1970 was 1.2 (95% confidence interval 1.1 to 1.3). Similar patterns were also evident for mild pre-eclampsia, although attenuated. Changes in the population prevalence of obesity and smoking were associated with period and cohort trends in pre-eclampsia but did not explain the trends.
Conclusions Rates of severe pre-eclampsia have been increasing in the United States and age-period-cohort effects all contribute to these trends. Although smoking and obesity have driven these trends, changes in the diagnostic criteria may have also contributed to the age-period-cohort effects. Health consequences of rising obesity rates in the United States underscore that efforts to reduce obesity may be beneficial to maternal and perinatal health.
doi:10.1136/bmj.f6564
PMCID: PMC3898425  PMID: 24201165
7.  Cardiovascular mortality after pre-eclampsia in one child mothers: prospective, population based cohort study 
Objective To assess the association of pre-eclampsia with later cardiovascular death in mothers according to their lifetime number of pregnancies, and particularly after only one child.
Design Prospective, population based cohort study.
Setting Medical Birth Registry of Norway.
Participants We followed 836 147 Norwegian women with a first singleton birth between 1967 and 2002 for cardiovascular mortality through linkage to the national Cause of Death Registry. About 23 000 women died by 2009, of whom 3891 died from cardiovascular causes. Associations between pre-eclampsia and cardiovascular death were assessed by hazard ratios, estimated by Cox regression analyses. Hazard ratios were adjusted for maternal education (three categories), maternal age at first birth, and year of first birth
Results The rate of cardiovascular mortality among women with preterm pre-eclampsia was 9.2% after having only one child, falling to 1.1% for those with two or more children. With term pre-eclampsia, the rates were 2.8% and 1.1%, respectively. Women with pre-eclampsia in their first pregnancy had higher rates of cardiovascular death than those who did not have the condition at first birth (adjusted hazard ratio 1.6 (95% confidence interval 1.4 to 2.0) after term pre-eclampsia; 3.7 (2.7 to 4.8) after preterm pre-eclampsia). Among women with only one lifetime pregnancy, the increase in risk of cardiovascular death was higher than for those with two or more children (3.4 (2.6 to 4.6) after term pre-eclampsia; 9.4 (6.5 to 13.7) after preterm pre-eclampsia). The risk of cardiovascular death was only moderately elevated among women with pre-eclamptic first pregnancies who went on to have additional children (1.5 (1.2 to 2.0) after term pre-eclampsia; 2.4 (1.5 to 3.9) after preterm pre-eclampsia). There was little evidence of additional risk after recurrent pre-eclampsia. All cause mortality for women with two or more lifetime births, who had pre-eclampsia in first pregnancy, was not elevated, even with preterm pre-eclampsia in first pregnancy (1.1 (0.87 to 1.14)).
Conclusions Cardiovascular death in women with pre-eclampsia in their first pregnancy is concentrated mainly in women with no additional births. This association might be due to health problems that discourage or prevent further pregnancies rather than to pre-eclampsia itself. As a screening criterion for cardiovascular disease risk, pre-eclampsia is a strong predictor primarily among women with only one child—particularly with preterm pre-eclampsia.
doi:10.1136/bmj.e7677
PMCID: PMC3508198  PMID: 23186909
8.  The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women 
Bjog  2010;117(7):821-829.
Objective
To examine the relationship between dietary supplement use during pregnancy and birth outcomes.
Design
A prospective birth cohort.
Setting
Leeds, UK.
Sample
One thousand two hundred and seventy-four pregnant women aged 18–45 years.
Methods
Dietary supplement intake was ascertained using three questionnaires for the first, second and third trimesters. Dietary intake was reported in a 24-hour dietary recall administered by a research midwife at 8–12 weeks of gestation. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records.
Main outcome measures
Birthweight, birth centile and preterm birth.
Results
Reported dietary supplement use declined from 82% of women in the first trimester of pregnancy to 22% in the second trimester and 33% in the third trimester. Folic acid was the most commonly reported supplement taken. Taking any type of daily supplement during any trimester was not significantly associated with size at birth taking into account known relevant confounders. Women taking multivitamin-mineral supplements in the third trimester were more likely to experience preterm birth (adjusted OR = 3.4, 95% CI 1.2, 9.6, P= 0.02).
Conclusions
Regular multivitamin–mineral supplement use during pregnancy, in a developed country setting, is not associated with size at birth. However, it appears to be associated with preterm birth if taken daily in the third trimester. The mechanism for this is unclear and our study’s findings need confirming by other cohorts and/or trials in developed countries.
doi:10.1111/j.1471-0528.2010.02549.x
PMCID: PMC2874518  PMID: 20353456
Birthweight; dietary supplements; pregnancy; pregnancy outcome; preterm birth
9.  The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study in British women 
Objective
To examine the relationship between dietary supplement use during pregnancy and birth outcomes.
Design
A prospective birth cohort.
Setting
Leeds, UK.
Sample
One thousand two hundred and seventy-four pregnant women aged 18–45 years.
Methods
Dietary supplement intake was ascertained using three questionnaires for the first, second and third trimesters. Dietary intake was reported in a 24-hour dietary recall administered by a research midwife at 8–12 weeks of gestation. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records.
Main outcome measures
Birthweight, birth centile and preterm birth.
Results
Reported dietary supplement use declined from 82% of women in the first trimester of pregnancy to 22% in the second trimester and 33% in the third trimester. Folic acid was the most commonly reported supplement taken. Taking any type of daily supplement during any trimester was not significantly associated with size at birth taking into account known relevant confounders. Women taking multivitamin-mineral supplements in the third trimester were more likely to experience preterm birth (adjusted OR = 3.4, 95% CI 1.2, 9.6, P = 0.02).
Conclusions
Regular multivitamin–mineral supplement use during pregnancy, in a developed country setting, is not associated with size at birth. However, it appears to be associated with preterm birth if taken daily in the third trimester. The mechanism for this is unclear and our study's findings need confirming by other cohorts and/or trials in developed countries.
doi:10.1111/j.1471-0528.2010.02549.x
PMCID: PMC2874518  PMID: 20353456
Birthweight; dietary supplements; pregnancy; pregnancy outcome; preterm birth
10.  Born Toon Soon: Care before and between pregnancy to prevent preterm births: from evidence to action 
Reproductive Health  2013;10(Suppl 1):S3.
Providing care to adolescent girls and women before and between pregnancies improves their own health and wellbeing, as well as pregnancy and newborn outcomes, and can also reduce the rates of preterm birth. This paper has reviewed the evidence based interventions and services for preventing preterm births; reported the findings from research priority exercise; and prescribed actions for taking this call further. Certain factors in the preconception period have been shown to increase the risk for prematurity and, therefore, preconception care services for all women of reproductive age should address these risk factors through preventing adolescent pregnancy, preventing unintended pregnancies, promoting optimal birth spacing, optimizing pre-pregnancy weight and nutritional status (including a folic acid containing multivitamin supplement, and ensuring that all adolescent girls have received complete vaccination. Preconception care must also address risk factors that may be applicable to only some women. These include screening for and management of chronic diseases, especially diabetes; sexually-transmitted infections; tobacco and smoke exposure; mental health disorders, notably depression; and intimate partner violence. The approach to research in preconception care to prevent preterm births should include a cycle of development and delivery research that evaluates how best to scale up coverage of existing, evidence-based interventions, epidemiologic research that assesses the impact of implementing these interventions, and discovery science that better elucidates the complex causal pathway of preterm birth and helps to develop new screening and intervention tools. In addition to research, policy and financial investment is crucial to increasing opportunities to implement preconception care, and rates of prematurity should be included as a tracking indicator in global and national maternal child health assessments.
Declaration
This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth (ISBN 978 92 4 150343 30). The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format.
doi:10.1186/1742-4755-10-S1-S3
PMCID: PMC3828587  PMID: 24625189
11.  Poor pregnancy outcome in women with type 1 diabetes is predicted by elevated HbA1c and spikes of high glucose values in the third trimester 
Objective
To analyse data from a randomised, controlled study of prandial insulin aspart versus human insulin, both with NPH insulin, in pregnant women with type 1 diabetes for potential factors predicting poor pregnancy outcomes.
Research design/method
Post hoc analysis including 91 subjects randomised prior to pregnancy with known outcome in early pregnancy and 259 subjects randomised prior to pregnancy/during pregnancy of <10 weeks’ gestation with known late-pregnancy outcomes. Poor early-pregnancy outcomes included fetal loss <22 gestational weeks and/or congenital malformation (n = 18). Poor late-pregnancy outcomes included: composite endpoint including pre-eclampsia, preterm delivery and perinatal death (n = 78); preterm delivery (n = 63); and excessive fetal growth (n = 88).
Results
18 patients experienced a malformed/lost fetus in early pregnancy – none preceded by severe hypoglycaemia. Albuminuria in early pregnancy was a significant predictor of poor late-pregnancy outcome (composite endpoint; p = 0.012). In the third trimester, elevated HbA1c, ≥ 1 plasma glucose (PG) measurement >11 mmol/L (198 mg/dL) and %PG values outside 3.9–7.0 mmol/L (70–126 mg/dL) were significant predictors of poor late-pregnancy outcomes (all p < 0.05).
Conclusions
Elevated HbA1c, high glucose spikes and out-of-range %PG in the third trimester, and albuminuria in early pregnancy, are associated with poor late-pregnancy outcomes.
doi:10.3109/14767058.2013.806896
PMCID: PMC3877859  PMID: 23687948
HbA1c; glucose spikes; predictors; pregnancy outcome
12.  Socio-demographic characteristics of women sustaining injuries during pregnancy: a study from the Danish National Birth Cohort 
BMJ Open  2012;2(4):e000826.
Objectives
To describe adverse birth outcomes associated with hospital-treated injuries that took place among women in the Danish National Birth Cohort.
Design
Longitudinal cohort study.
Setting
Denmark.
Participants
90 452 women and their offspring selected from the Danish National Birth Cohort.
Primary and secondary outcome measures
To determine if injured women were more likely to deliver an infant preterm, with low birth weight, stillborn or have a spontaneous abortion, the authors estimated HRs. ORs were generated to assess APGAR scores and infants born small for gestational age (SGA). Models were adjusted for maternal smoking and drinking during pregnancy, household socioeconomic status, eclampsia/pre-eclampsia or gestational diabetes status during pregnancy and maternal age at birth; estimates for preterm birth were also adjusted for prior history of preterm birth.
Results
In the cohort of 90 452 pregnant women, 3561 (3.9%) received medical treatment for an injury during pregnancy. Injured pregnant women were more likely to deliver infants that were stillborn or have pregnancies terminated by spontaneous abortion. The authors did not detect an adverse effect between injuries sustained during pregnancy and delivery of preterm, low birth weight or SGA infants, or infants with an APGAR score of <7.
Conclusions
The study shows that injuries occurring among women from an unselected population may not have an adverse effect on birth weight, gestational age, APGAR score or SGA status but may adversely affect the risk of stillbirth and spontaneous abortions in some situations.
Article summary
Article focus
We describe adverse birth outcomes associated with injuries that took place among pregnant women in the Danish National Birth Cohort and include in our assessment injury severity, cause and mechanism.
Key messages
Injured pregnant women were more likely to deliver infants that were stillborn or have pregnancies that were terminated by spontaneous abortion. We did not detect an adverse effect between injuries sustained during pregnancy and delivery of preterm, low birth weight or SGA infants, or infants with an APGAR score of <7.
Women sustaining head or neck injuries were more likely to deliver an infant SGA and have a stillbirth, though these results were not statistically significant.
Strengths and limitations of this study
Previous studies have selected pregnant trauma patients or emergency room patients; our study, however, presents injuries among pregnant women from a general population.
We only have data on late spontaneous abortions, and if injured fetuses are aborted early, we would not detect an association.
doi:10.1136/bmjopen-2012-000826
PMCID: PMC3391365  PMID: 22761281
13.  Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial 
Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk.
Design Randomised, blinded, placebo controlled clinical trial.
Setting Tertiary public hospital in Mexico City.
Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery.
Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy.
Main outcome measure Development of pre-eclampsia/eclampsia.
Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14).
Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined.
Trial registration Clinical trials NCT00469846.
doi:10.1136/bmj.d2901
PMCID: PMC3100912  PMID: 21596735
14.  MATERNAL IRON STATUS: RELATION TO FETAL GROWTH, LENGTH OF GESTATION AND THE NEONATE’S IRON ENDOWMENT 
Nutrition reviews  2011;69(Suppl 1):S23-S29.
Anemia prevalence is highest in preschool children, reproductive age women and women who are pregnant. While etiology is multifactorial, a deficiency in iron is the most commonly recognized nutritional cause. Observational studies imply that supplementation with iron or iron-folic acid should be started early in pregnancy, if not before, in order to prevent low birth weight and preterm delivery. Despite this clinical trials, even those from early pregnany, are equivocal. Recent follow up studies of children born to iron-folic acid supplemented women suggest that mortality is decreased and that the infant’s iron endowment reflects the mother’s iron status during pregnancy.
doi:10.1111/j.1753-4887.2011.00429.x
PMCID: PMC3227006  PMID: 22043878
iron deficiency; anemia; pregnancy
15.  The risk of adverse pregnancy outcomes in women who are overweight or obese 
Background
The prevalence of obesity amongst women bearing children in Australia is rising and has important implications for obstetric care. The aim of this study was to assess the prevalence and impact of mothers being overweight and obese in early to mid-pregnancy on maternal, peripartum and neonatal outcomes.
Methods
A secondary analysis was performed on data collected from nulliparous women with a singleton pregnancy enrolled in the Australian Collaborative Trial of Supplements with antioxidants Vitamin C and Vitamin E to pregnant women for the prevention of pre-eclampsia (ACTS). Women were categorized into three groups according to their body mass index (BMI): normal (BMI 18.5-24.9 kg/m2); overweight (BMI 25-29.9 kg/m2) and; obese (BMI 30-34.9 kg/m2). Obstetric and perinatal outcomes were compared by univariate and multivariate analyses.
Results
Of the 1661 women included, 43% were overweight or obese. Obese women were at increased risk of pre-eclampsia (relative risk (RR) 2.99 [95% confidence intervals (CI) 1.88, 4.73], p < 0.0001) and gestational diabetes (RR 2.10 [95%CI 1.17, 3.79], p = 0.01) compared with women with a normal BMI. Obese and overweight women were more likely to be induced and require a caesarean section compared with women of normal BMI (induction - RR 1.33 [95%CI 1.13, 1.57], p = 0.001 and 1.78 [95%CI 1.51, 2.09], p < 0.0001, caesarean section - RR 1.42 [95%CI 1.18, 1.70], p = 0.0002 and 1.63 [95%CI 1.34, 1.99], p < 0.0001). Babies of women who were obese were more likely to be large for gestational age (LFGA) (RR 2.08 [95%CI 1.47, 2.93], p < 0.0001) and macrosomic (RR 4.54 [95%CI 2.01, 10.24], p = 0.0003) compared with those of women with a normal BMI.
Conclusion
The rate of overweight and obesity is increasing amongst the Australian obstetric population. Women who are overweight and obese have an increased risk of adverse pregnancy outcomes. In particular, obese women are at increased risk of gestational diabetes, pregnancy induced hypertension and pre-eclampsia. Effective preventative strategies are urgently needed.
Trial Registration
Current Controlled Trials ISRCTN00416244
doi:10.1186/1471-2393-10-56
PMCID: PMC2949787  PMID: 20849609
16.  Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial 
Background
Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term.
Methods/Design
Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised.
Discussion
This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity.
Trial Registration
NTR1792 Clinical trial registration: http://www.trialregister.nl
doi:10.1186/1471-2393-11-50
PMCID: PMC3161905  PMID: 21736705
17.  Antiplatelet agents for prevention of pre-eclampsia and its consequences: a systematic review and individual patient data meta-analysis 
Background
There is now good evidence that antiplatelet agents (principally low dose aspirin) prevent pre-eclampsia, a leading cause of morbidity and mortality for pregnant women and their babies. A Cochrane Review identified moderate, but clinically important, reductions in the relative risks of pre-eclampsia (19%), preterm birth (7%) and perinatal mortality (16%) in women allocated antiplatelets, rather than placebo or no antiplatelet.
Uncertainty remains, however, about whether some women (in terms of risk) benefit more than others, what dose of aspirin is best and when in pregnancy treatment should ideally start. Rather than undertake new trials, the best way to answer these questions is to utilise existing individual patient data from women enrolled in each trial.
Methods/Design
Systematic review with meta-analysis based on individual patient data. This involves the central collection, validation and re-analysis of thoroughly checked data from individual women in all the available randomised trials.
The objective is to confirm that antiplatelet agents, given during pregnancy, will reduce the incidence of pre-eclampsia. The review will then determine the size of this effect, and whether antiplatelets delay the onset of pre-eclampsia or its impact on important outcomes for women and their babies. It will also explore whether the effect of antiplatelets differs by womens' risk profile; when commenced during pregnancy; and/or by dose.
Discussion
The PARIS (Perinatal Antiplatelet Review of International Studies) Collaboration has been formed to undertake the review. This will be the first individual patient data review in the perinatal field. Final results should be available by 2006–7.
doi:10.1186/1471-2393-5-7
PMCID: PMC555958  PMID: 15833147
18.  Maternal and neonatal outcomes of hospital vaginal deliveries in Tibet 
Introduction
To determine the outcomes of vaginal deliveries in three study hospitals in Lhasa, Tibet Autonomous Region (TAR), People's Republic of China (PRC), at high altitude (3,650 m).
Methods
Prospective observational study of 1,121 vaginal deliveries.
Results
Pre-eclampsia/gestational hypertension (PE/GH) was the most common maternal complication 18.9% (n=212), followed by postpartum hemorrhage (blood loss ≥ 500 ml) 13.4%. There were no maternal deaths. Neonatal complications included: low birth weight (10.2%), small for gestational age (13.7%), preterm delivery (4.1%) and low Apgar (3.7%). There were 11 stillbirths (9.8/1,000 live births) and 19 early neonatal deaths (17/1,000 live births).
Conclusion
This is the largest study of maternal and newborn outcomes in Tibet. It provides information on the outcomes of institutional vaginal births among women delivering infants at high altitude. There was a higher incidence of PE/GH and low birth weight; rates of PPH were not increased compared to those at lower altitudes.
doi:10.1016/j.ijgo.2007.03.033
PMCID: PMC2194809  PMID: 17481630
Postpartum hemorrhage; maternal mortality; Tibet; high altitude; pre-eclampsia; gestational hypertension
19.  Correlates of intake of folic acid-containing supplements among pregnant women 
Objective
This study describes the timing and correlates of folic acid supplement intake among pregnant women.
Study design
Data from 2518 women with estimated delivery dates from 1997 to 2000, collected for the National Birth Defects Prevention Study, a population-based case-control study, were analyzed. Multinomial logistic regression was used to identify correlates of supplement intake.
Results
Fifty-three percent of women began taking folic acid supplement during the periconceptional period, 35% during early pregnancy, and 8% during late pregnancy (ie, 3 months before through 1 month after conception, 2–3 months after conception, or more than 3 months after conception, respectively). Women who did not take folic acid supplement periconccptionally tended to be nonwhite, speak Spanish, have low education, be younger than 25 years old. be nulliparous, smoke, have no previous miscarriage and no fertility treatments, begin prenatal care and become aware of their pregnancy after the first trimester, have nonplanned pregnancies, and eat less breakfast cereal.
Conclusion
This study identifies correlates of folic acid supplement intake, which may contribute to the design of interventions to improve intake during early pregnancy.
doi:10.1016/j.ajog.2005.06.018
PMCID: PMC1775038  PMID: 16389033
Folic acid; Supplements; Pregnancy
20.  Effect of lycopene in prevention of preeclampsia in high risk pregnant women 
Objective
To evaluate the effect of pre-natal supplementation of antioxidant Lycopene in prevention of pre-eclampsia in the high risk pregnant women. We also assessed the effect of lycopene supplementation on intra-uterine growth restriction and the perinatal outcome in women at high risk of developing pre-eclampsia.
Materials and Methods
A total of 54 women between 14–28 weeks of pregnancy who were at high risk of developing pre-eclampsia were considered for the study. Inclusion criteria were women with a previous history of preeclampsia, a growth-retarded fetus, perinatal death, multifetal gestation and chronic hypertension. Of the total of 54 women, 30 women were randomized to receive Lycopene in a dose of 2 mg twice daily starting from the date of entry and were instructed to continue the drug regularly until delivery. The other 24 women were randomized to the control group and they did not take lycopene. The controls were matched to cases with respect to the risk factors for the development of preeclampsia. Both groups were followed at monthly intervals. In addition, a Doppler assessment for evidence of intrauterine growth retardation was done at around 28 wks of gestation. Data regarding development of preeclampsia, period of gestation during delivery, mode of delivery, fetal weight and perinatal outcome were recorded and subjected to statistical analysis.
Results
Of the 30 women randomized to receive the drug, ten women were lost to follow-up. Thus only 20 women in the treatment group completed the study. All the 24 women in the control group completed the study. Lycopene was not found to decrease the incidence of pre-eclampsia in high risk women. Women in the lycopene supplementation group had significantly lesser incidence of growth restricted babies and had a significantly better perinatal outcome compared to women in the placebo group.
Conclusion
Lycopene supplementation does not decrease the incidence of preeclampsia in high risk women. However lycopene supplementation does seem to help in reducing the incidence of intra-uterine growth restriction.
doi:10.5152/jtgga.2011.08
PMCID: PMC3939288  PMID: 24591955
Preeclampsia; anti-oxidants; intrauterine growth restriction
21.  Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth: A Cohort Study 
PLoS Medicine  2009;6(5):e1000061.
In an analysis of a cohort of pregnant women, Radek Bukowski and colleagues describe an association between taking folic acid supplements and a reduction in the risk of preterm birth.
Background
Low plasma folate concentrations in pregnancy are associated with preterm birth. Here we show an association between preconceptional folate supplementation and the risk of spontaneous preterm birth.
Methods and Findings
In a cohort of 34,480 low-risk singleton pregnancies enrolled in a study of aneuploidy risk, preconceptional folate supplementation was prospectively recorded in the first trimester of pregnancy. Duration of pregnancy was estimated based on first trimester ultrasound examination. Natural length of pregnancy was defined as gestational age at delivery in pregnancies with no medical or obstetrical complications that may have constituted an indication for delivery. Spontaneous preterm birth was defined as duration of pregnancy between 20 and 37 wk without those complications. The association between preconceptional folate supplementation and the risk of spontaneous preterm birth was evaluated using survival analysis. Comparing to no supplementation, preconceptional folate supplementation for 1 y or longer was associated with a 70% decrease in the risk of spontaneous preterm delivery between 20 and 28 wk (41 [0.27%] versus 4 [0.04%] spontaneous preterm births, respectively; HR 0.22, 95% confidence interval [CI] 0.08–0.61, p = 0.004) and a 50% decrease in the risk of spontaneous preterm delivery between 28 and 32 wk (58 [0.38%] versus 12 [0.18%] preterm birth, respectively; HR 0.45, 95% CI 0.24–0.83, p = 0.010). Adjustment for maternal characteristics age, race, body mass index, education, marital status, smoking, parity, and history of prior preterm birth did not have a material effect on the association between folate supplementation for 1 y or longer and spontaneous preterm birth between 20 and 28, and 28 to 32 wk (adjusted HR 0.31, 95% CI 0.11–0.90, p = 0.031 and 0.53, 0.28–0.99, p = 0.046, respectively). Preconceptional folate supplementation was not significantly associated with the risk of spontaneous preterm birth beyond 32 wk. The association between shorter duration (<1 y) of preconceptional folate supplementation and the risk of spontaneous preterm birth was not significant after adjustment for maternal characteristics. However, the risk of spontaneous preterm birth decreased with the duration of preconceptional folate supplementation (test for trend of survivor functions, p = 0.01) and was the lowest in women who used folate supplementation for 1 y or longer. There was also no significant association with other complications of pregnancy studied after adjustment for maternal characteristics.
Conclusions
Preconceptional folate supplementation is associated with a 50%–70% reduction in the incidence of early spontaneous preterm birth. The risk of early spontaneous preterm birth is inversely proportional to the duration of preconceptional folate supplementation. Preconceptional folate supplementation was specifically related to early spontaneous preterm birth and not associated with other complications of pregnancy.
Editors' Summary
Background
Most pregnancies last about 40 weeks, but sometimes the new family member arrives early. Every year, half a million babies in the United States (12.5% of all babies) are born prematurely (before 37 completed weeks of pregnancy). Sadly, premature babies are more likely to die than full-term babies and many have short- and/or long-term health problems. Premature babies often have breathing problems, they are susceptible to life-threatening infections, and they are more likely to have learning and developmental disabilities than those born on time. The severity of these health problems depends on the degree of prematurity—preterm babies born between 34 and 36 weeks of pregnancy rarely develop severe disabilities, but a quarter of babies born before 28 weeks of pregnancy develop serious lasting disabilities and half have learning and behavioral problems. Although doctors have identified some risk factors for early delivery (for example, smoking), it is impossible to predict who will have an early birth and there is no effective way to prevent preterm births.
Why Was This Study Done?
Some researchers think that folate supplements may prevent preterm births. Folate (folic acid), a vitamin found in leafy green vegetables, fruits, and dried beans, helps to prevent neural tube birth defects. Consequently, women are encouraged to take folic acid supplements throughout (and preferably before) pregnancy and many governments now mandate that bread, pasta, and other grain products be fortified with folic acid to help women get sufficient folate. There is some evidence that women who deliver early have less folate in their blood than women who deliver at term. Furthermore, folate supplementation during pregnancy has increased the length of pregnancy in some but not all clinical trials. A possible explanation for these mixed results is that the duration of pregnancy reflects conditions in the earliest stages of pregnancy or before conception and that folate supplementation needs to start before conception to reduce the risk of preterm birth. In this study, the researchers test this idea by analyzing data collected from nearly 35,000 pregnant women enrolled in a study that was originally designed to investigate screening for Down's syndrome.
What Did the Researchers Do and Find?
During the first three months of their pregnancy, the women were asked whether they had taken folate supplements before conception. The duration of each pregnancy was estimated from ultrasound measurements taken early in the pregnancy and from the time of delivery. During the study, 1,658 women had spontaneous preterm deliveries before 37 weeks and 160 delivered before 32 weeks. After allowing for other maternal characteristics that might have affected the likelihood of preterm delivery, the risk of spontaneous preterm delivery between 20 and 28 weeks was 70% lower in women who took folate supplements for more than a year before becoming pregnant than in women who didn't take a supplement. Long-term folate supplementation also reduced the risk of preterm delivery between 28 and 32 weeks by 50% but did not affect the risk of preterm birth beyond 32 weeks. Folate supplementation for less than a year before conception did not reduce the risk of preterm birth, and folate supplementation was not associated with any other complications of pregnancy.
What Do These Findings Mean?
These findings show that folate supplementation for a year or more before conception is associated with a 50%–70% decrease in early (but not late) spontaneous preterm births and that the longer a woman takes folate supplements before becoming pregnant, the lower her risk of a preterm birth. Although the researchers allowed for maternal characteristics that might have affected the duration of pregnancy, it is possible that folate supplementation may not be responsible for the reduction in preterm birth risk seen in this study. For example, taking folate supplements may be a marker of healthy behavior and the women taking the supplements might have been doing something else that was reducing their risk of preterm birth. However, despite this and other limitations of this study, these findings suggest that long-term folate supplementation before conception is worth investigating further as a potential way to prevent preterm births.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000061.
This study is further discussed in a PLoS Medicine Perspective by Nicholas Fisk
The MedlinePlus encyclopedia contains a page on premature babies (in English and Spanish); MedlinePlus provides links to other information on premature babies (in English and Spanish)
The US National Institute of Child Health and Human Development provides information on preterm labor and birth
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth and on folic acid (in English and Spanish)
The Nemours Foundation, another nonprofit organization for child health, also provides information on premature babies (in English and Spanish)
The US Office of Dietary Supplements has a fact sheet on folate
doi:10.1371/journal.pmed.1000061
PMCID: PMC2671168  PMID: 19434228
22.  Risk of pre-eclampsia in first and subsequent pregnancies: prospective cohort study 
Objective To investigate whether pre-eclampsia is more common in first pregnancies solely because fewer affected women, who presumably have a higher risk of recurrence, go on to have subsequent pregnancies.
Design Prospective cohort study.
Setting Swedish Medical Birth Register.
Participants 763 795 primiparous mothers who had their first births in Sweden, 1987-2004.
Main outcome measures Pre-eclampsia.
Results The risk of pre-eclampsia was 4.1% in the first pregnancy and 1.7% in later pregnancies overall. However, the risk was 14.7% in the second pregnancy for women who had had pre-eclampsia in their first pregnancy and 31.9% for women who had had pre-eclampsia in the previous two pregnancies. The risk for multiparous women without a history of pre-eclampsia was around 1%. The incidence of pre-eclampsia associated with delivery before 34 weeks’ gestation was 0.42% in primiparous women, 0.11% in multiparous women without a history of pre-eclampsia, and 6.8% and 12.5% in women who had had one or two previous pregnancies affected, respectively. The proportion of women who went on to have a further pregnancy was 4-5% lower after having a pregnancy with any pre-eclampsia but over 10% lower if pre-eclampsia was associated with very preterm delivery. The estimated risk of pre-eclampsia in parous women did not change with standardisation for pregnancy rates.
Conclusions Having pre-eclampsia in one pregnancy is a poor predictor of subsequent pregnancy but a strong predictor for recurrence of pre-eclampsia in future gestations. The lower overall risk of pre-eclampsia among parous women was not explained by fewer conceptions among women who had had pre-eclampsia in a previous gestation. Early onset pre-eclampsia might be associated with a reduced likelihood of a future pregnancy and with more recurrences than late onset pre-eclampsia when there are further pregnancies. Findings are consistent with the existence of two distinct conditions: a severe recurrent early onset type affected by chronic factors, genetic or environmental, and a milder sporadic form affected by transient factors.
doi:10.1136/bmj.b2255
PMCID: PMC3269902  PMID: 19541696
23.  Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study 
BMJ : British Medical Journal  2001;323(7323):1213-1217.
Objective
To assess whether mothers and fathers have a higher long term risk of death, particularly from cardiovascular disease and cancer, after the mother has had pre-eclampsia.
Design
Population based cohort study of registry data.
Subjects
Mothers and fathers of all 626 272 births that were the mothers' first deliveries, recorded in the Norwegian medical birth registry from 1967 to 1992. Parents were divided into two cohorts based on whether the mother had pre-eclampsia during the pregnancy. Subjects were also stratified by whether the birth was term or preterm, given that pre-eclampsia might be more severe in preterm pregnancies.
Main outcome measures
Total mortality and mortality from cardiovascular causes, cancer, and stroke from 1967 to 1992, from data from the Norwegian registry of causes of death.
Results
Women who had pre-eclampsia had a 1.2-fold higher long term risk of death (95% confidence interval 1.02 to 1.37) than women who did not have pre-eclampsia. The risk in women with pre-eclampsia and a preterm delivery was 2.71-fold higher (1.99 to 3.68) than in women who did not have pre-eclampsia and whose pregnancies went to term. In particular, the risk of death from cardiovascular causes among women with pre-eclampsia and a preterm delivery was 8.12-fold higher (4.31 to 15.33). However, these women had a 0.36-fold (not significant) decreased risk of cancer. The long term risk of death was no higher among the fathers of the pre-eclamptic pregnancies than the fathers of pregnancies in which pre-eclampsia did not occur.
Conclusions
Genetic factors that increase the risk of cardiovascular disease may also be linked to pre-eclampsia. A possible genetic contribution from fathers to the risk of pre-eclampsia was not reflected in increased risks of death from cardiovascular causes or cancer among fathers.
What is already known on this topicMaternal and fetal genes (including those inherited from the father) may contribute to pre-eclampsia, which occurs in 3-5% of pregnanciesOne set of candidate genes for pre-eclampsia is the maternal genes for thrombophilia, which may increase the mother's risk of death from cardiovascular diseaseWhat this study addsWomen who have pre-eclampsia during a pregnancy that ends in a preterm delivery have an eightfold higher risk of death from cardiovascular disease compared with women who do not have pre-eclampsia and whose pregnancy goes to termFathers of pregnancies in which pre-eclampsia occurred have no increased risk of death from cardiovascular diseaseThese results are compatible with maternal genes for thrombophilia having an effect on the risk of pre-eclampsia and of death from cardiovascular disease
PMCID: PMC59993  PMID: 11719411
24.  Impact of micronutrient supplementation during pregnancy on birth weight, duration of gestation, and perinatal mortality in rural western China: double blind cluster randomised controlled trial 
Objective To examine the impact of antenatal supplementation with multiple micronutrients or iron and folic acid compared with folic acid alone on birth weight, duration of gestation, and maternal haemoglobin concentration in the third trimester.
Design Cluster randomised double blind controlled trial.
Setting Two rural counties in north west China.
Participants 5828 pregnant women and 4697 live births.
Interventions Villages were randomised for all pregnant women to take either daily folic acid (control), iron with folic acid, or multiple micronutrients with a recommended allowance of 15 vitamins and minerals.
Main outcome measures Birth weight, length, and head circumference measured within 72 hours after delivery. Neonatal survival assessed at the six week follow-up visit.
Results Birth weight was 42 g (95% confidence interval 7 to 78 g) higher in the multiple micronutrients group compared with the folic acid group. Duration of gestation was 0.23 weeks (0.10 to 0.36 weeks) longer in the iron-folic acid group and 0.19 weeks (0.06 to 0.32 weeks) longer in the multiple micronutrients group. Iron-folic acid was associated with a significantly reduced risk of early preterm delivery (<34 weeks) (relative risk 0.50, 0.27 to 0.94, P=0.031). There was a significant increase in haemoglobin concentration in both iron-folic acid (5.0 g/l, 2.0 to 8.0 g/l, P=0.001) and multiple micronutrients (6.9 g/l, 4.1 to 9.6 g/l, P<0.001) groups compared with folic acid alone. In post hoc analyses there were no significant differences for perinatal mortality, but iron-folic acid was associated with a significantly reduced early neonatal mortality by 54% (relative risk 0.46, 0.21 to 0.98).
Conclusion In rural populations in China antenatal supplementation with iron-folic acid was associated with longer gestation and a reduction in early neonatal mortality compared with folic acid. Multiple micronutrients were associated with modestly increased birth weight compared with folic acid, but, despite this weight gain, there was no significant reduction in early neonatal mortality. Pregnant women in developing countries need sufficient doses of iron in nutrient supplements to maximise reductions in neonatal mortality.
Trial registration ISRCTN08850194.
doi:10.1136/bmj.a2001
PMCID: PMC2577799  PMID: 18996930
25.  Factors associated with prenatal folic acid and iron supplementation among 21,889 pregnant women in Northern Tanzania: A cross-sectional hospital-based study 
BMC Public Health  2012;12:481.
Background
Folate and iron deficiency during pregnancy are risk factors for anaemia, preterm delivery, and low birth weight, and may contribute to poor neonatal health and increased maternal mortality. The World Health Organization recommends supplementation of folic acid (FA) and iron for all pregnant women at risk of malnutrition to prevent anaemia. We assessed the use of prenatal folic acid and iron supplementation among women in a geographical area with a high prevalence of anaemia, in relation to socio-demographic, morbidity and health services utilization factors.
Methods
We analysed a cohort of 21,889 women who delivered at Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania, between 1999 and 2008. Logistic regression models were used to describe patterns of reported intake of prenatal FA and iron supplements.
Results
Prenatal intake of FA and iron supplements was reported by 17.2% and 22.3% of pregnant women, respectively. Sixteen percent of women reported intake of both FA and iron. Factors positively associated with FA supplementation were advanced maternal age (OR = 1.17, 1.02-1.34), unknown HIV status (OR = 1.54, 1.42-1.67), a diagnosis of anaemia during pregnancy (OR = 12.03, 9.66-14.98) and indicators of lower socioeconomic status. Women were less likely to take these supplements if they reported having had a malaria episode before (OR = 0.57, 0.53-0.62) or during pregnancy (OR = 0.45, 0.41-0.51), reported having contracted other infectious diseases (OR = 0.45, 0.42-0.49), were multiparous (OR = 0.73, 0.66-0.80), had preeclampsia/eclampsia (OR = 0.48, 0.38-0.61), or other diseases (OR = 0.55, 0.44-0.69) during pregnancy. Similar patterns of association emerged when iron supplementation alone and supplementation with both iron and FA were evaluated.
Conclusions
FA and iron supplementation are low among pregnant women in Northern Tanzania, in particular among women with co-morbidities before or during pregnancy. Attempts should be made to increase supplementation both in general and among women with pregnancy complications.
doi:10.1186/1471-2458-12-481
PMCID: PMC3438116  PMID: 22734580
Folic acid; Iron; Supplement; Pregnant women; Tanzania

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