Keywords

1 Background

The pregnancy booking visit affords the health-care professional an opportunity to assess a pregnant woman’s risk of PTB, among other potential adverse pregnancy outcomes. This guidance is aimed to facilitate early identification of women likely to experience PTB, especially in LMICs settings, and to highlight risk factors for PTB that should signpost care pathways to try to reduce the risk and improve birth outcomes. A woman’s body mass index (BMI) and nutritional status, covered in this section, affect her risk of spontaneous PTB and should be assessed.

2 Evidence Statement

  • Iron, folic acid, and calcium (in specific contexts) are necessary supplements for pregnancy in general and also have potential benefits for reducing the risk of PTB. In undernourished populations, balanced energy and protein dietary supplementation, as well as nutrition education, is recommended for pregnant women to improve broad pregnancy outcomes. Likewise, for populations at risk of low levels of vitamin D, supplementation may be recommended to improve general pregnancy outcomes.

  • The benefit of other micronutrients, vitamins, and minerals to reduce the risk of PTB is unclear. Low-certainty evidence links low dietary zinc to PTB risks, but there is no definitive evidence in support of routine zinc supplementation for all pregnant women. However, in settings where there are low dietary or maternal zinc levels, women may benefit from zinc supplementation. Nutrition is a marker of general health and until clearer evidence is available regarding the benefit of supplementing with specific nutrients, caregivers should explore and address access to balanced diets and food security in general during the pregnancy risk assessment.

3 Synopsis of best Evidenced Nutrition-Related Risk Factors for Preterm Birth

For a summary of the evidence of these nutrition-related risk factors for preterm birth, please see Table 1, in Sect. 5, below.

Table 1 Summary of evidenced risk factors and interventions for PTB
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3.1 Body Mass Index (BMI)

  1. (i)

    Low BMI.

    Low BMI is associated with an increased risk of PTB (BMI <19 kg/m2 relative risk (RR): 1.29, 95% CI: 1.15–1.46) [1, 2]. A systematic review of 78 studies involving 1,025,794 women found that the overall risk of PTB was increased in underweight women (adjusted RR 1.29, 95% CI 1.15–1.46), as were the risks of spontaneous PTB (adjusted RR 1.32, 95% CI 1.10–1.57) and induced PTB (adjusted RR 1.21, 95% CI 1.07–1.36) [2]. However, when limited to developing countries (5/52, 10% of cohort studies), no significant association was found (RR: 0.99, 95% CI: 0.67–1.45) [2].

  2. (ii)

    High BMI.

    Overweight (OR 1.20, 95% CI 1.04–1.38), obese (OR 1.60, 95% CI 1.32–1.94), and morbidly obese (OR 2.42, 95% CI 1.46–4.05) have been shown to increase risks of PTB [15]. Data from LMICs is absent. In one systematic review on maternal BMI which included 39 studies (1,788,633 women), findings suggested that obese women (BMI, 35–40) have an increased risk for PTB in general (aOR = 1.33, 95% CI: 1.12–1.57), as well as for moderate (aOR = 2.43, 95% CI: 1.46–4.05) and very PTB (AOR = 1.96, 95% CI: 1.66–2.31). Very obese women (BMI > 40) have an even higher risk (AOR = 2.27, 95%CI: 1.76–2.94) [5].

3.2 Dietary Patterns

A systematic review of observational studies on maternal dietary patterns and birth outcomes found that unhealthy dietary patterns characterized by high intakes of refined grains, processed meat, and foods high in saturated fat or sugar were associated with a trend towards a higher risk of PTB (OR: 1.17; 95% CI: 0.99, 1.39; I2 = 76%). Healthy dietary patterns—characterized by high intakes of vegetables, fruits, whole grains, low-fat dairy, and lean protein foods—were associated with a lower risk of PTB (OR for top compared with bottom tercile: 0.79; 95% CI: 0.68, 0.91; I2 = 32%) [7].

3.3 Nutrient and Mineral Deficiencies Definitely Associated with an Increased Risk of Preterm Birth

Observational studies suggest that pre-conceptional and periconceptional intake of some vitamin and mineral supplements are associated with a reduced risk of PTB [8]. Further evidence examines specific supplements for nutrient deficiencies:

  1. (i)

    Maternal Anemia and/or Iron Deficiency.

    • A meta-analysis of 18 prospective and retrospective studies with a combined sample size of 932,090 showed a significant relationship between maternal anemia during pregnancy and PTB (OR 1.56 [95% CI: 1.25–1.95]) [16].

    • WHO guidelines recommend daily oral iron but suggest that weekly iron should be considered for a) cases where daily iron is not acceptable due to side effects and b) populations with anemia in pregnancy prevalence of less than 20% (as this is not considered public health risk) [3].

  2. (ii)

    Folic Acid.

    • Evidence that folic acid supplementation reduces the risk of PTB is conflicting [17], with one systematic review suggesting that supplementation is associated with a significant reduction in the risk of PTB only when being initiated after conception [12]. However, folate supplementation has established benefits for reducing birth defects.

  3. (iii)

    Calcium.

    • The WHO recommends that in populations with low dietary calcium intake pregnant women should receive daily calcium supplementation to reduce the risk of pre-eclampsia [3].

    • One review found that high-dose calcium supplementation (at least 1 g/day) may reduce the risk of pre-eclampsia and PTB, particularly for women with low calcium diets (low-quality evidence) [13]. The average risk of PTB was reduced in the calcium supplementation group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; low-quality evidence); this reduction was greatest among women at higher risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83). Most studies were carried out in LMIC settings [13].

    • A review examining the effect of calcium supplementation on pregnancy outcomes other than hypertension and pre-eclampsia showed no clear additional benefits on preventing PTB [14]. However, when evidence is stratified by dose (<1000 mg vs ≥1000 mg), high-dose calcium supplementation appears to reduce PTB (12 trials, 15,479 women; RR: 0.81, 95% CI: 0.66–0.99) [3]. Current WHO guidelines recommend calcium supplementation only to reduce the risk of developing pregnancy-induced hypertension [3, 14].

3.4 Nutrient and Mineral Deficiencies Possibly Associated with an Increased Risk of Preterm Birth in Specific Situations

Supplementing the following nutrient factors is not clearly established to reduce the risk of PTB. However, for some of these factors, the evidence is conflicting, and for others, further research is required.

  1. (i)

    Vitamin D.

    • The WHO does not recommend vitamin D supplementation to improve maternal and perinatal outcomes, advising that sunlight is the most important source of vitamin D [3]. In some countries such as the UK, supplementation with 10 micrograms of vitamin D per day for population groups at increased risk of vitamin D deficiency (those with darker skin or experiencing low sunlight exposure) and pregnant and lactating women is recommended [11].

    • Evidence (22 trials, 3725 pregnant women) suggests that supplementation with vitamin D alone during pregnancy probably reduces the risk of pre-eclampsia, gestational diabetes, and low birthweight but may make little or no difference to the risk of having PTB (RR 0.66, 95% CI 0.34 to 1.30; 7 trials, 1640 women) [18]. An earlier review (9 trials, 1916 pregnant women) suggests that supplementation with vitamin D combined with calcium may reduce the risk for pre-eclampsia but may actually increase the risk of PTB (RR 1.52, 95% CI 1.01 to 2.28; 5 trials, 942 women), consistent with an earlier version [19] which it updated which showed that the combination increased the risk of delivery prior to 37 weeks of gestation compared to women who received no treatment or placebo (RR 1.57; 95% CI 1.02 to 2.43; 3 studies, 798 women, moderate quality), but that supplementation of vitamin D alone reduces the risk of PTB compared to no intervention or placebo (8.9% versus 15.5%; RR 0.36; 95% CI 0.14 to 0.93; 3 trials, 477 women, moderate quality). These reviews included studies from LMIC settings (Bangladesh, India, Brazil, Iran) [18, 19].

    • Given conflicting findings between systematic reviews of observational studies and those examining the effectiveness of vitamin D from randomized control trials (RCTs) which showed no effect, it is suggested that low vitamin D levels may reflect poor general maternal health status for which attention to general health rather than vitamin D supplementation is required [20].

  2. (ii)

    Zinc.

    • Maternal zinc supplementation is contentious—while WHO guidelines recommend further research regarding zinc supplementation for pregnant women [3], low-to-moderate-certainty evidence suggests that zinc supplementation may reduce PTB (16 trials, 7637 women; RR: 0.86, 95% CI: 0.76–0.97) in women with presumed low zinc intake or poor nutrition (14 trials mostly from LMIC settings, 7099 women; RR: 0.87, 95% CI: 0.77–0.98) [21], rather than as a routine supplement for all pregnant women.

  3. (iii)

    Vitamin B12.

    • A systematic review found that B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31) and PTB (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49) [22].

  4. (iv)

    Multiple Micronutrient (MMN) Supplements.

    • According to WHO guidelines, there is high-certainty evidence that shows that MMN supplements make little or no difference to PTB rates (14 trials; RR: 0.95, 95% CI: 0.88–1.03) [3]. However, recent evidence indicates that MMN (added to iron and folic acid) may slightly reduce the risk of PTB (average RR 0.95, 95% CI 0.90 to 1.01; 18 trials, 91,425 participants; moderate-quality evidence) and very PTB (average RR 0.81, 95% CI 0.71 to 0.93; 4 trials, 37,701 participants) when compared to iron, with or without folic acid [23].

  5. (v)

    Vitamin A.

    • Vitamin A deficiency is not linked to PTB and is not generally recommended in pregnancy as it can be teratogenic [11]. However, it is appropriate to supplement pregnant women in areas where vitamin A deficiency is a severe public health problem, to prevent night blindness [3].

  6. (vi)

    Omega-3 Fatty Acids.

    • One systematic review of RCTs has shown that women who received omega-3 LCPUFA experienced less PTB < 37 weeks (13.4% versus 11.9%; RR 0.89, 95% CI 0.81 to 0.97; 26 RCTs, 10,304 participants; high-quality evidence) and early PTB < 34 weeks (4.6% versus 2.7%; RR 0.58, 95% CI 0.44 to 0.77; 9 RCTs, 5204 participants; high-quality evidence) than those who did not receive omega-3 [24].

  7. (vii)

    Restricting Coffee Intake.

    • Low-certainty evidence from one trial suggests that restricting caffeine intake may have little or no effect on PTB (1153 neonates; RR: 0.81, 95% CI: 0.48–1.37); however, those with high intake are recommended to reduce it for better pregnancy outcomes in general [3]. Some studies indicate that high caffeine consumption is associated with low birth weight and/or prematurity [25].

3.5 Nutrient and Mineral Deficiencies Not Shown to be Associated with an Increased Risk of Preterm Birth [3]

Supplementation is not recommended for vitamin B6 (pyridoxine), vitamin E and C (moderate-certainty evidence shows little or no effect on PTB; 11 trials, 20,565 neonates; RR: 0.98, 95% CI: 0.88–1.09), and high protein (1 study, 505 women; RR: 1.14, 95% CI: 0.83–1.56).

4 Practical Clinical Risk Assessment Instructions for PTB

As part of the general evaluation of pregnant women, some routine nutritional assessment is carried out during antenatal booking in most contexts. However, information obtained is seldom employed to undertake a formal risk assessment for PTB. Therefore, we highlight below routine data that should be collected to enable formal evaluation of a women’s risk of PTB.

  • BMI: Low and high body mass index (BMI) are risk factors for PTB. Maternal weight and height should be measured at the booking appointment, and the woman’s BMI should be calculated.

  • Dietary patterns: A well-balanced diet during pregnancy may reduce risk of PTB. Knowledge of and access to a well-balanced diet should be assessed during pregnancy.

Nutrient and mineral deficiencies: Iron deficiency anemia is a risk for PTB. Pregnant women should be offered screening for anemia early in pregnancy and at 28 weeks when other blood screening tests are being performed [11]. In a context where calcium deficiency may exist, or risk of pre-eclampsia is deemed substantial, or there is suspicion of low dietary calcium levels, calcium supplementation should be offered. Populations at high risk of vitamin D deficiency should be offered vitamin D supplementation to improve pregnancy outcomes generally.

5 Evidenced Risk Factors and Interventions for PTB

These are outlined in Table 1.

6 Summary of Nutrition Interventions to Reduce PTB

These are shown in Table 2.

Table 2 Benefit statements of nutrition interventions to reduce preterm birth
Full size table

7 Research and Clinical Practice Recommendation

To clarify outcomes for PTB, further RCTs are recommended that target populations with a high prevalence of vitamin D deficiency. It would be helpful if future trials were to evaluate whether the increase of serum 25-hydroxyvitamin D concentration supplementation early in pregnancy is associated with improved maternal and infant outcomes in populations with different BMI, skin pigmentation, vitamin D status, and setting [18]. Research should also evaluate the PTB risk of combining calcium and vitamin D. Further research is also required to look at zinc and omega-3 fatty acids in relation to PTB.

However, the most important focus should be on promoting a good quality diet in general, rather than a specific supplementation regime. Studies to address ways of improving the overall nutritional status of populations in impoverished areas, rather than focusing on micronutrient and or zinc supplementation, are required [21]. The role of maternal BMI on PTB risks in LMICs warrants further study.