Influence of maternal nutrition on outcome of pregnancy: prospective cohort study

ObjectiveTo investigate the relations of maternal diet and smoking during pregnancy to placental and birth weights at term.DesignProspective cohort study.SettingDistrict general hospital in the south of England.Participants693 pregnant nulliparous white women with singleton pregnancies who were selected from antenatal booking clinics with stratified random sampling.ResultsPlacental and birth weights were unrelated to the intake of any macronutrient. Early in pregnancy, vitamin C was the only micronutrient independently associated with birth weight after adjustment for maternal height and smoking. Each ln mg increase in vitamin C was associated with a 50.8 g (95% confidence interval 4.6 g to 97.0 g) increase in birth weight. Vitamin C, vitamin E, and folate were each associated with placental weight after adjustment for maternal characteristics. In simultaneous regression, however, vitamin C was the only nutrient predictive of placental weight: each ln mg increase in vitamin C was associated with a 3.2% (0.4 to 6.1) rise in placental weight. No nutrient late in pregnancy was associated with either placental or birth weight.ConclusionsConcern over the impact of maternal nutrition on the health of the infant has been premature. Maternal nutrition, at least in industrialised populations, seems to have only a small effect on placental and birth weights. Other possible determinants of fetal and placental growth should be investigated.

Key messages

• Placental and infant birth weights were not associated with the intake of any macronutrient early or later in pregnancy
• After adjustment for the effects of maternal height and smoking, only vitamin C independently predicted birth weight. The expected mean difference in birth weight for infants with mothers in the upper and lower thirds of intake was about 70 g
• Vitamin C was the only nutrient that independently predicted placental weight, but again this relation was of doubtful clinical significance
• Among relatively well nourished women in industrialised countries, maternal nutrition seems to have only a marginal impact on infant and placental size. Other causes of variation in the size of clinically normal infants should now be investigated

     

Size at birth,maternal nutritional status in pregnancy,and blood pressure at age 17: population based analysis.

OBJECTIVE: To assess the effect of size at birth, maternal nutrition, and body mass index on blood pressure in late adolescence. DESIGN: Population based analysis of birth weight corrected for gestational age, mother''s weight before pregnancy and weight gain in pregnancy, obtained from the Jerusalem perinatal study, and blood pressure and body mass index at age 17, available from military draft records. SETTING: Jerusalem, Israel. SUBJECTS: 10,883 subjects (6684 men and 4199 women) born in Jerusalem during 1974-6 and subsequently drafted to the army. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures measured at age 17 and their correlation with birth weight, size at birth, mother''s body mass index and weight gain during pregnancy, and height and weight at age 17. RESULTS: Systolic and diastolic blood pressures were significantly and positively correlated with body weight, height, body mass index at age 17, and with mother''s body weight and body mass index before pregnancy, but not with birth weight or mother''s weight gain in pregnancy. CONCLUSION: Variables reflecting poor intrauterine nutrition, including low maternal body mass index before pregnancy, poor maternal weight gain in pregnancy, and being born small for gestational age, were not associated with a higher blood pressure in late adolescence.     

Mothers' birth weight and survival of their offspring: population based study.

OBJECTIVE: To test the hypothesis that a baby''s survival is related to the mother''s birth weight. DESIGN: Population based dataset for two generations. SETTING: Population registry in Norway. SUBJECTS: All birth records for women born in Norway since 1967 were linked to births during 1981-94, thereby forming 105104 mother-offspring units. MAIN OUTCOME MEASURES: Perinatal mortality specific for weight for offspring in groups of maternal birth weight (with 500 g categories in both). RESULTS: A mother''s birth weight was strongly associated with the weight of her baby. Maternal birth weight was associated with perinatal survival of her baby only for mothers with birth weights under 2000 g. These mothers were more likely to lose a baby in the perinatal period (odds ratio 2.3, 95% confidence interval 1.4 to 3.7). Among mothers with a birth weight over 2000 g there was no overall association between mother''s weight and infant survival. There was, however, a strong interaction between mother''s birth weight, infant birth weight, and infant survival. Mortality among small babies was much higher for those whose mothers had been large at birth. For example, babies weighing 2500-2999 g had a threefold higher mortality if their mother''s birth weight had been high (> or = 4000 g) than if the mother had been small (2500-2999 g). CONCLUSION: Mothers who weighed less than 2000 g at birth have a higher risk of losing their own babies. For mothers who weighed > or = 2000 g their birth weight provides a benchmark for judging the growth of their offspring. Babies who are small relative to their mother''s birth weight are at increased risk of mortality.     

Cotyledon and binucleate cell nitric oxide synthase expression in an ovine model of fetal growth restriction.

Heat exposure early in ovine pregnancy results in placental insufficiency and intrauterine growth restriction (PI-IUGR). We hypothesized that heat exposure in this model disrupts placental structure and reduces placental endothelial nitric oxide synthase (eNOS) protein expression. We measured eNOS protein content and performed immunohistochemistry for eNOS in placentas from thermoneutral (TN) and hyperthermic (HT) animals killed at midgestation (90 days). Placental histomorphometry was compared between groups. Compared with the TN controls, the HT group showed reduced delivery weights (457 +/- 49 vs. 631 +/- 21 g; P < 0.05) and a trend for reduced placentome weights (288 +/- 61 vs. 554 +/- 122 g; P = 0.09). Cotyledon eNOS protein content was reduced by 50% in the HT group (P < 0.03). eNOS localized similarly to the vascular endothelium and binucleated cells (BNCs) within the trophoblast of both experimental groups. HT cotyledons showed a reduction in the ratio of fetal to maternal stromal tissue (1.36 +/- 0.36 vs. 3.59 +/- 1.2; P< or = 0.03). We conclude that eNOS protein expression is reduced in this model of PI-IUGR and that eNOS localizes to both vascular endothelium and the BNC. We speculate that disruption of normal vascular development and BNC eNOS production and function leads to abnormal placental vascular tone and blood flow in this model of PI-IUGR.     

Effect of heat stress on ovine placental growth in early pregnancy.

Ditocous Dorset ewes were fed to predicted requirements and kept in environmental chambers at 21 degrees C (n = 6) or 40 degrees C (n = 5) between days 50 and 75 of gestation. Ewes were slaughtered and the pregnant uterus was dissected for measurement of conceptus weights and in vitro estimations of placental mitotic activity. Heat caused a 19% reduction in placental weight but did not affect fetal weight. Placental DNA and protein concentrations and protein/DNA were similar in both groups. Total placental DNA content was significantly reduced in the heated ewes, suggesting a reduction in cell number; however, DNA synthetic rate tended to be higher. These results are consistent with the hypothesis that fetal growth retardation in chronically heat-stressed ewes occurs in late pregnancy as a consequence of a primary reduction in placental growth in early gestation.     

Placental growth, angiogenic gene expression, and vascular development in undernourished adolescent sheep

Limiting maternal nutrient intake during ovine adolescent pregnancy progressively depleted maternal body reserves, impaired fetal nutrient supply, and slowed fetal soft tissue growth. The present study examined placental growth, angiogenic gene expression, and vascular development in this undernourished adolescent model at Days 90 and 130 of gestation. Singleton pregnancies were established, and ewes were offered an optimal control (C; n = 14) or low (L [0.7 x C]; n = 21) dietary intake. Seven ewes receiving L intakes were switched to C intakes on Day 90 of gestation (L-C). Fetal body weight (P < 0.01) and glucose concentrations (P < 0.03) were reduced in L versus C pregnancies by Day 130, whereas L-C group values were intermediate. Placental cellular proliferation, gross morphology, and mass were independent of maternal nutrition at both Day 90 and 130. In contrast, capillary area density in the maternal caruncular portion of the placentome was reduced by 20% (P < 0.001) at both stages of gestation in L compared with C groups. Caruncular capillary area density was equivalent in the L and L-C groups at Day 130. Placental mRNA expression of five key angiogenic ligands or receptors increased (P < 0.001) between Days 90 and 130 of gestation. VEGFA mRNA expression was higher (P < 0.04) in L compared with C and L-C pregnancies at Day 130, but otherwise gene expression of the remaining angiogenic factors and receptors analyzed was unaffected by maternal intake. Undernourishing the pregnant adolescent dam restricts fetal growth independently of changes in placental mass. Alterations in maternal placental vascular development may, however, play a role in mediating the previously reported reduction in maternal and hence fetal nutrient supply.     

Does early nutrition in infants born before term programme later blood pressure?

OBJECTIVES--To test whether nutrition early in infants'' development programmes later blood pressure and whether the reported relation between low birth weight and later high blood pressure is due to poor nutrition or growth before full term. DESIGN--Prospective randomisation of preterm infants to early diets differing greatly in nutrient content in four parallel multicentre trials, with blinded follow up 7.5-8 years later. SETTING--Neonatal units at Cambridge, Ipswich, King''s Lynn, Norwich, and Sheffield. SUBJECTS--758 children weighing under 1850 g at birth. MAIN OUTCOME MEASURE--Blood pressure at age of 7.5-8 years. RESULTS--There were major differences in nutrient intake from randomised diets (preterm formula v standard formula and preterm formula v donor breast milk; in each case with or without mother''s milk), but follow up showed no differences in later blood pressure. Individual subjects showed large variation in protein and energy intakes and in growth performance, including degrees of growth failure seldom seen in utero, but these factors were also unrelated to later blood pressure. CONCLUSION--Extremes of nutritional intake and growth performance in preterm infants do not programme later blood pressure at 7.5-8 years of age. These findings do not support the hypothesis that high blood pressure has early nutritional origins. We suggest that the long term rise in blood pressure reported in individuals who had low birthweight (at full term) is not, as previously speculated, due to poor fetal nutrition or growth as such.     

Air pollution-induced placental epigenetic alterations in early life: a candidate miRNA approach

Particulate matter (PM) exposure during in utero life may entail adverse health outcomes in later-life. Air pollution's adverse effects are known to alter gene expression profiles, which can be regulated by microRNAs (miRNAs). We investigate the potential influence of air pollution exposure in prenatal life on placental miRNA expression. Within the framework of the ENVIRONAGE birth cohort, we measured the expression of six candidate miRNAs in placental tissue from 210 mother-newborn pairs by qRT-PCR. Trimester-specific PM_2.5 exposure levels were estimated for each mother's home address using a spatiotemporal model. Multiple regression models were used to study miRNA expression and in utero exposure to PM_2.5 over various time windows during pregnancy. The placental expression of miR-21 (?33.7%, 95% CI: ?53.2 to ?6.2, P = 0.022), miR-146a (?30.9%, 95% CI: ?48.0 to ?8.1, P = 0.012) and miR-222 (?25.4%, 95% CI: ?43.0 to ?2.4, P = 0.034) was inversely associated with PM_2.5 exposure during the 2nd trimester of pregnancy, while placental expression of miR-20a and miR-21 was positively associated with 1st trimester exposure. Tumor suppressor phosphatase and tensin homolog (PTEN) was identified as a common target of the miRNAs significantly associated with PM exposure. Placental PTEN expression was strongly and positively associated (+59.6% per 5 µg/m³ increment, 95% CI: 26.9 to 100.7, P < 0.0001) with 3rd trimester PM_2.5 exposure. Further research is required to establish the role these early miRNA and mRNA expression changes might play in PM-induced health effects. We provide molecular evidence showing that in utero PM_2.5 exposure affects miRNAs expression as well as its downstream target PTEN.     

200例先天性尿道下裂患儿的临床特征及其危险因素分析

目的:研究200例先天性尿道下裂患儿的临床特征及其危险因素。方法:选择2016年1月~2019年12月我院收治的先天性尿道下裂患儿200例进行研究,记作观察组,另取同期于我院接受体检的健康儿童200例作为对照组,分析观察组患儿的临床分型情况,比较两组儿童父母的一般情况、儿童出生情况,并采用多因素Logistic回归分析先天性尿道下裂的影响因素。结果:200例先天性尿道下裂患儿临床分型按照占比从高到低的顺序依次为阴茎体型46.50%(93/200)、阴茎阴囊型28.00%(56/200)、冠状沟型17.00%(34/200)、阴囊型4.50%(9/200)、阴茎头型3.00%(6/200)、会阴型1.00%(2/200)。观察组父亲生活性接触化学物、母亲流产史、母亲孕期饮食缺乏肉类、母亲孕期饮食缺乏鱼类、母亲孕期应用保胎药、母亲孕期吸烟或被动吸烟人数占比均高于对照组(均P<0.05)。观察组早产、低出生体重人数占比高于对照组(均P<0.05)。经多因素Logistic回归分析显示,父亲生活性接触化学物、母亲流产史、母亲孕期饮食缺乏肉类、母亲孕期饮食缺乏鱼类、母亲孕期应用保胎药、母亲孕期吸烟或被动吸烟、早产、低出生体重均是先天性尿道下裂的危险因素(均P<0.05)。结论:先天性尿道下裂患儿临床分型以阴茎体型为主,双亲不良生活习惯、化学物接触史以及早产、低出生体重均是先天性尿道下裂的危险因素,值得临床重点关注。     

Mother's weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study.

OBJECTIVE: To determine whether restricted growth in utero is associated with an increased risk of coronary heart disease are among men in Finland, where rates of the disease are among the highest in the world. DESIGN: Follow up study. SETTING: Helsinki, Finland. SUBJECTS: 3302 men born in Helsinki University Central Hospital during 1924-33 who went to school in the city of Helsinki and were resident in Finalnd in 1971. MAIN OUTCOME MEASURES: Standardised mortality ratios for coronary heart disease. RESULTS: Men who were thin at birth, with low placental weight, had high death rates from coronary heart disease. Men whose mothers had a high body mass index in pregnancy also had high death rates. In a multivariate analysis the hazard ratio for coronary heart disease was 1.37 (95% confidence interval 1.20 to 1.57) (P < 0.0001) for every standard deviation decrease in ponderal index at birth and 1.24 (1.10 to 1.39) (P = 0.0004) for every standard deviation increase in mother''s body mass index. The effect of mother''s body mass index was restricted to mothers of below average stature. CONCLUSION: These findings suggest a new explanation for the epidemics of coronary heart disease that accompany Westernisation. Chronically malnourished women are short and light and their babies tend to be thin. The immediate effect of improved nutrition is that women become fat, which seems to increase the risk of coronary heart disease in the next generation. With continued improvements in nutrition, women become taller and heavier; their babies are adequately nourished; and maternal fatness no longer increases the risk of coronary heart disease, which therefore declines.     

The relationship between plasma oestrone sulphate concentrations in pregnant dairy cattle and calf birth weight, calf viability, placental weight and placental expulsion

A total of 54 Holstein-Friesian cows (13 primiparous and 41 multiparous) was used to study maternal plasma oestrone sulphate (E1S) during pregnancy and its relationship to birth weight and viability of calves and time required for placental expulsion after calving. Plasma samples were obtained from the tail vein of cows once every month from days 90 to 180, every 2 weeks from days 181 to 270, and every day from day 270 of gestation to parturition. The E1S concentrations were measured by radioimmunoassay, and birth weight, placental measurements, neonatal viability and the period from calving to placental expulsion were recorded. E1S concentrations were correlated positively (0.71 > or = r > or = 0.32, P < 0.05 or P < 0.01) with calf birth weight and weights of cotyledons, intercotyledonary membranes and total placenta from days 210 of gestation to 1 day prepartum. Calf birth weight was correlated positively (p < 0.01) with the weight of the cotyledons (r = 0.87), intercotyledonary membranes (r = 0.78) and total placenta (r = 0.88). In addition, E1S concentrations were positively correlated (0.63 > or = r > or = 0.28, P < 0.05 or P < 0.01) with the neonatal viability after day 195 of pregnancy, and were negatively correlated (-0.29 > or = r > or = -0.55, P < 0.05 or P < 0.01) with the intervals from parturition to placental expulsion after 225 days of pregnancy. The results suggest that variation among dams for circulating E1S levels during late pregnancy may be caused by variation of placental development and ability for oestrogen production and conjugation, and they may influence fetal growth, neonatal viability and retained placenta.     

Morphology and morphometry of in vivo- and in vitro-produced bovine concepti from early pregnancy to term and association with high birth weights

This study was designed to characterize conceptus development based on pre- and postnatal measurements of in vivo- and in vitro-derived bovine pregnancies. In vivo-produced embryos were obtained after superovulation, whereas in vitro-produced embryos were derived from established procedures for bovine IVM, IVF and IVC. Blastocysts were transferred to recipients to obtain pregnancies of single (in vivo/singleton or in vitro/singleton groups) or twin fetuses (in vitro/twins group). Ultrasonographic examinations were performed weekly, from Day 30 of gestation through term. Videotaped images were digitized, and still-frames were used for the measurement of conceptus traits. Calves and fetal membranes (FM) were examined and measured upon delivery. In vitro-produced fetuses were smaller than in vivo controls (P < 0.05) during early pregnancy (Day 37 to Day 58), but in vitro/singletons presented significantly higher weights at birth than in vivo/control and in vitro/twin calves (P < 0.05). From late first trimester of pregnancy (Day 72 to Day 93), placentomes surrounding in vitro-derived singleton fetuses were longer and thinner than controls (P < 0.05). At term, the presence of giant cotyledons in the fetal membranes in the in vitro group was associated with a larger cotyledonary surface area in the fetal horn (P < 0.05). The biphasic growth pattern seen in in vitro-produced pregnancies was characterized by conceptus growth retardation during early pregnancy, followed by changes in the development of the placental tissue. Resulting high birth weights may be a consequence of aberrant placental development due to the disruption of the placental restraint on fetal growth toward the end of pregnancy.     

Relationship between placental vascular endothelial growth factor expression and placental/endometrial vascularity in the pig

We investigated the temporal association between placental vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis and vascular permeability, and changes in placental/endometrial vascularity on selected days throughout gestation in the pig. Placental and endometrial tissues were collected from sows on Days 25 (n = 4), 36 (n =6), 44 (n = 6), 70 (n =5), 90 (n =5 ), and 112 (n = 7) of gestation. Cross sections of the placental/endometrial interface of each conceptus were used to estimate the number of blood vessels per unit area via image analysis and the intensity of VEGF staining via immunohistochemistry. Placental tissues were also collected on these days to evaluate VEGF mRNA expression. Placental VEGF mRNA expression and the numbers of blood vessels per unit area of placental and adjacent endometrial tissue were low and decreasing from Day 25 to Day 44, before increasing (P < 0.05) markedly and progressively through Day 112. These data are consistent with the marked increase in VEGF immunostaining in the chorionic and uterine luminal epithelium from early to late gestation. Further, these increases in placental VEGF mRNA were positively correlated with fetal weight (r = 0.73; P < 0.0001) and placental efficiency (fetal weight/placental weight ratio; r = 0.66, P < 0.0001). These data are consistent with a role for VEGF in increasing the number of blood vessels at the placental endometrial interface, resulting in an increased capacity for nutrient transfer from the maternal to the fetal compartment.     

Switching maternal dietary intake at the end of the first trimester has profound effects on placental development and fetal growth in adolescent ewes carrying singleton fetuses.

The aim was to investigate whether placental growth and hence pregnancy outcome could be altered by switching adolescent dams from a high to a moderate nutrient intake, and vice-versa, at the end of the first trimester. Embryos recovered from adult ewes inseminated by a single sire were transferred in singleton to peripubertal adolescents. After transfer, adolescent ewes were offered a high (H, n = 33) or moderate (M, n = 32) level of a diet calculated to promote rapid or moderate maternal growth rates, respectively. At Day 50 of gestation, half the ewes had their dietary intakes switched, yielding 4 treatment groups: HH, MM, HM, and MH. A subset of ewes were killed at Day 104 of gestation to determine maternal body composition in relation to growth of the products of conception. Maternal body composition measurements revealed that the higher live weight in the high-intake dams was predominantly due to an increase in body fat deposition, with a less pronounced increase in body protein. At Day 104, HH and MH groups (high intake during second trimester) compared with MM and HM groups (moderate intake during second trimester) had a lower (p < 0.002) total fetal cotyledon weight; but fetal weight, conformation, and individual organ weights were not significantly influenced by maternal dietary intake. In ewes delivering live young at term, a high plane of nutrition from the end of the first trimester (HH and MH groups) compared with moderate levels (MM and HM groups) was associated with a reduction in gestation length (p < 0.009), total placental weight (p < 0.002), total fetal cotyledon weight (p < 0.001), and mean fetal cotyledon weight per placenta (p < 0.001). Fetal cotyledon number was dependent on maternal dietary intake during the first trimester only and was lower (p < 0.007) in HH and HM ewes compared to MM and MH ewes. The inhibition of fetal cotyledon growth in HH and MH groups was associated with a major decrease (p < 0.001) in lamb birth weight at term relative to the MM and HM groups. Thus, reducing maternal dietary intake from a high to a moderate level at the end of the first trimester stimulates placental growth and enhances pregnancy outcome, and increasing maternal dietary intake at this time point has a deleterious effect on placental development and fetal growth.     

Metals content in placentas from moderate cigarette consumers: correlation with newborn birth weight

Cigarette consumption during pregnancy produces deleterious effects in both, mother and fetus, some of them due to the presence of toxic elements in cigarette smoke, such as cadmium. Placenta constitutes a dual-purpose specimen for evaluating the pollutant burden exerted on the mother as well as on the fetus. The main objective of this study was to establish a correlation between placental concentration and distribution of some metal elements and birth weight of neonates delivered by mothers, who were either moderate smokers or nonsmokers. Forty nonsmoking and moderate smoking pregnant women paired per age, parity, weight, height and body mass index were selected. Smoking was assessed by self-reported cigarette consumption during pregnancy and urine cotinine concentration before delivery. Placental metal concentrations were evaluated by atomic absorption spectrometry (copper and cadmium) and neutron activation analysis (zinc and iron). Newborns from smokers had lower birth weights compared to infants from nonsmokers. Birth weights were correlated with placental cadmium concentrations in both, smokers and nonsmokers. Placental zinc and cadmium of smokers were mainly located at the maternal side and their levels were higher than those found in nonsmokers placentas. In addition, all metal nutrient/pollutant ratios were decreased in the smoker group. In this first study performed in our region, we found that moderate smoking mothers deliver neonates with decreased birth weight and highly correlated to placental cadmium concentration. Decreased metal nutrient/pollutant ratios, a condition here found in smokers, may indicate a placental dysfunction, contributing to impair birth weight.     

Late but not early gestational maternal growth hormone treatment increases fetal adiposity in overnourished adolescent sheep

In the overnourished adolescent sheep, maternal tissue synthesis is promoted at the expense of placental growth and leads to a major decrease in lamb birth weight at term. Maternal growth hormone (GH) concentrations are attenuated in these pregnancies, and it was recently demonstrated that exogenous GH administration throughout the period of placental proliferation stimulates uteroplacental and fetal development by Day 81 of gestation. The present study aimed to determine whether these effects persist to term and to establish whether GH affects fetal growth and body composition by increasing placental size or by altering maternal metabolism. Adolescent recipient ewes were implanted with singleton embryos on Day 4 postestrus. Three groups of ewes offered a high dietary intake were injected twice daily with recombinant bovine GH from Days 35 to 65 of gestation (high intake plus early GH) or from Days 95 to 125 of gestation (high intake plus late GH) or remained untreated (high intake only). A fourth moderate-intake group acted as optimally nourished controls. Pregnancies were terminated at Day 130 of gestation (6 per group) or were allowed to progress to term (8-10 per group). GH administration elevated maternal plasma concentrations of GH, insulin, glucose, and nonesterified fatty acids during the defined treatment windows, while urea concentrations were decreased. At Day 130, GH treatment had reduced the maternal adiposity score, percentage of fat in the carcass, and internal fat depots and leptin concentrations, predominantly in the high-intake plus late GH group. Placental weight was lower in high-intake vs. control dams but independent of GH treatment. In contrast, fetal weight was elevated by late GH treatment, and these fetuses had higher relative carcass fat content, perirenal fat mass, and liver glycogen concentrations than all other groups. Expression of leptin mRNA in fetal perirenal fat and fetal plasma leptin concentrations were not significantly altered by maternal nutritional intake or GH. In pregnancies proceeding to term, the duration of gestation, fetal placental mass, and lamb birth weight were reduced in high-intake compared with control dams but were not significantly affected by GH treatment. In conclusion, exogenous GH has profound effects on maternal endocrinology, metabolism, and body composition when administered during early and late pregnancy. Treatment during late pregnancy has a modest effect on fetal growth independent of placental size and a profound effect on fetal adiposity, which may have implications beyond the fetal period.     

Consequences of gestational malaria on birth weight: finding the best timeframe for intermittent preventive treatment administration

To investigate the consequences of intermittent preventive treatment (IPTp) timing on birth weight, we pooled data from two studies conducted in Benin between 2005 and 2010: a prospective cohort of 1037 pregnant women and a randomised trial comparing sulfadoxine-pyrimethamine (SP) to mefloquine in 1601 women. A total of 1439 women (752 in the cohort and 687 in the SP arm of the randomised trial) who delivered live singletons were analysed. We showed that an early intake of the first SP dose (4 months of gestation) was associated with a lower risk of LBW compared to a late intake (6-7 months of gestation) (aOR = 0.5 p = 0.01). We also found a borderline increased risk of placental infection when the first SP dose was administered early in pregnancy (aOR = 1.7 p = 0.1). This study is the first to investigate the timing of SP administration during pregnancy. We clearly demonstrated that women who had an early intake of the first SP dose were less at risk of LBW compared to those who had a late intake. Pregnant women should be encouraged to attend antenatal visits early to get their first SP dose and a third dose of SP could be recommended to cover the whole duration of pregnancy and to avoid late infections of the placenta.