PROTOCOL: Effects of preconception care and periconception interventions on maternal nutritional status and birth outcomes in low‐ and middle‐income countries: A systematic review

Interest in preconception health for maximising gains for mothers and babies started with the release of the seminal report from Centre for Disease Control (Johnson et al., 2006). Further, in 2011, the World Health Organisation (WHO) convened a meeting of experts where there was an overwhelming agreement on the potential for preconception care to have a positive impact on maternal and child health outcomes (World Health Organisation, 2013). Since then there is growing awareness of the importance of the preconception period and efforts have been made to increase awareness and promote reproductive health from adolescents onwards. Preconception care is important for healthy maternal, birth, and neonatal health outcomes (Dean et al., 2013). Optimising a woman's health before planning and conceiving pregnancy is increasingly recognised as an important strategy to enhance maternal and child health (Dean, Imam, Lassi and Bhutta, 2013). Preconception period is an ideal time to introduce interventions relating to nutrition and other lifestyle factors to promote health and for ensuring good pregnancy preparedness. Since 99% of all maternal and newborn deaths occur in low- and middle-income countries (LMICs; World Health Organisation, 2017), early start of preconception care particularly for girls living in LMICs is very crucial. At present, policies and guidelines on preconception care are scarce and the care starts when the women becomes pregnant and extends to childbirth and postnatal period (for mothers and babies). There is a clear gap in the continuum of care, particularly for young girls who enters the reproductive years and women who are not pregnant. These girls and women receives little to no attention until their first pregnancy. Evidence also suggests that antenatal care is often too late to revert the detrimental health risks and issues that may have on developing foetus (Dean et al., 2013). Adolescents face multiple challenges to their health and social well being if they become pregnant early in life. Approximately 13% of all maternal mortality occurs in adolescents (World Health Organisation, 2014). The risk of maternal mortality is approximately five times higher for adolescents under the age of 15 years and twice as high for adolescents between 15 and 19 years of age compared with women aged 20–29 years (Nove, Matthews, Neal, & Camacho, 2014). These girls are at a higher risk for developing hypertension during pregnancy, severe anaemia, bleeding and infection. Because their pelvis has not yet grown large enough for the baby to pass through the birth canal, hence they have higher risk of obstructed labour, stillbirths; and their newborns are also more likely to be born prematurely, have low birth weight, or die in the first month of life (Gibbs, Wendt, Peters, & Hogue, 2012; Paranjothy, Broughton, Adappa, & Fone, 2009; World Health Organisation, 2007). These risks are further exacerbated by factors such as poverty, illiteracy, limited access to health care, lack of social support from family and absence of autonomy for decision-making (Nove et al., 2014). Apart from direct health consequences to the mother and baby, early motherhood is often linked to school drop-out, social difficulties and poor socioeconomic status (Penman-Aguilar, Carter, Snead, & Kourtis, 2013). They also have higher odds of experiencing depressive symptoms including loneliness, sleep disorders, loss of appetite and even thoughts of harming oneself or the baby within the 3 months after birth (Reid & Meadows-Oliver, 2007). The evidence further details that children born to teenage mothers tend to have poor health, poor cognitive development, behavioural problems and poor educational outcomes; they also have a high probability of becoming a teen parent themselves (Black et al., 2002). Therefore, it is important to encourage the use of contraceptives and educate the importance of planning pregnancy and delaying first pregnancy until the woman is at least 18 years of age which allows a woman's body to fully mature. Maternal nutritional deficiencies particularly iron and folate are common in LMICs. Anaemia in women from LMICs is due to low dietary intake of bioavailable iron combined with endemic infectious diseases such as helminthiasis, which puts women at increased risk during pregnancy. Low preconception haemoglobin and ferritin levels increase the risk of poor foetal growth and low birth weight (Dean, Lassi, Imam, & Bhutta, 2014a). Similarly, folate deficiency can lead to the development of neural tube defects (NTDs) in the foetus. Other micronutrients such as zinc, vitamin B and calcium have been found to improve maternal and newborn outcomes when supplementation is provided during pregnancy; however, their impact during the preconception period has not been established (Ramakrishnan, Grant, Goldenberg, Zongrone, & Martorell, 2012). Improved reproductive health and planning is the fundamental component of preconception care and starting early interventions such essential nutritional supplements in the preconception period can help women begin her pregnancy in the best of her health. Each year an estimated 140 million births take place (World Health Organisation, 2018). Of these 16 million occur to adolescents between the ages of 15–19 years and approximately 2.5 million to girls less than 16 years of age (World Health 2018, 2018). It is therefore important to delay the age at first pregnancy and optimise the interpregnancy intervals and make a healthy start when pregnancy is planned by supplementing essential micronutrients. Many adverse maternal, neonatal and pregnancy outcomes may be avoidable if the age at first pregnancy or optimising the gap between two pregnancies. Previous evidence has shown the benefits of delayed childbearing, specifically in adolescence, as adolescent pregnancy is known to be associated with an increased risk of preterm birth, stillbirth, small-for-gestational age, neonatal mortality, and complications during labour and delivery (Haldre, Rahu, Karro, & Rahu, 2007; Paranjothy et al., 2009; World Health Organisation, 2007). There is, however, variable evidence related to prolonging interpregnancy intervals. In a systematic review, Conde-Agudelo, Rosas-Bermudez, Castaño, and Norton (2012) identified that compared with interpregnancy intervals of 18–23 months, interpregnancy intervals shorter than 6 months were associated with increased risks of preterm birth, low birth weight and small-for-gestational age babies. While delaying the age of first pregnancy ensures the maturation and growth of the body, optimising pregnancy intervals gives time for body to recover and prepare itself for another pregnancy. This review will consider interventions to delay the age of first pregnancy or to optimise birth intervals. Interventions such as health education, contraception education and distribution, individual counselling, or sex education, and so forth. may be population-based, community-based, school based, hospital/clinic based targeting specific groups such as teenage or delivered by health professionals or workers. On the other hand, the benefits of micronutrient supplementation during pregnancy are well-established, particularly for iron and folic acid. There are numerous nutrition related interventions targeting different vitamins and nutrients to improve maternal and neonatal outcomes. Whilst folic acid may be one of the most widely known, there is evidence that multivitamins and other nutrients have a critical role in brain and nervous system development as well as impact the immune system during pregnancy, specifically relating to the inflammatory response (Ramakrishnan et al., 2012). Specifically, interventions have shown that vitamin A received during pregnancy may reduce maternal anaemia in women who likely have a vitamin A deficiency, however this review also demonstrated the vitamin A did not reduce maternal or newborn mortality (McCauley, van den Broek, Dou, & Othman, 2015). Another review investigating the use of supplementing pregnant women with vitamin D, demonstrated that vitamin D may reduce the risk of preeclampsia, low birth weight, and preterm birth (De-Regil, Palacios, Lombardo, & Peña-Rosas, 2016). There is also evidence for the use of multivitamin supplementation with iron and folic acid to reduce the risk of miscarriage (Balogun et al., 2016). However, there is limited evidence for micronutrient supplementation specifically during pre- and periconception apart from the use of folic acid, which has shown to reduce NTD (De-Regil, Peña-Rosas, Fernández-Gaxiola, & Rayco-Solon, 2015). The intermittent utilisation of iron and folic acid prior to conception has shown to reduce the risk of anaemia in reproductive age women, though additional evidence is needed to support improvements in other maternal and newborn outcomes (Fernández-Gaxiola & De-Regil, 2011). Ideally many of these interventions would have a preventive focus, for example, iron and folic acid supplementation, food fortification or dietary diversification to decrease the incidence of anaemia in women before they become pregnant. Pregnancy in the teenage years is associated with multiple risks and delaying the age of first pregnancy can reduce these risks. Interventions such as sex education and counselling at school and at community settings by peers and community health workers have shown impact (Brieger, Delano, Lane, Oladepo, & Oyedrian, 2001; García et al., 2012). Such interventions improve knowledge and promote attitudinal and behaviour change among young adolescents. These interventions also promote use of condoms and other birth control mechanism including abstinence (Cabezón et al., 2005). Interventions to delay pregnancy can include health education, contraception education and distribution, skills building and different forms of counselling (Oringanje et al., 2009). One intervention commonly utilised in LMICs is cash transfer programmes to encourage adolescent women to stay in school for longer and as a consequence avoid early marriage or sexual initiation (Baird, Chirwa, McIntosh, & Özler, 2010). A systematic review by Khan, Hazra, Kant, and Ali (2016) assessed the evidence for using conditional and unconditional cash transfers as a method to encourage contraceptive use in LMICs. The majority of the included studies utilised cash transfers to encourage school attendance or aimed to improve overall health and nutrition. While there were few available studies specifically targeting contraception, some studies did demonstrate a positive impact on contraceptive use and a decrease in fertility outcomes (i.e., number of pregnancies resulting in live births). Similarly, optimising the birth interval has shown positive impacts for mothers and babies (Afeworki, Smits, Tolboom, & van der Ven, 2015). Studies have long shown that interpregnancy intervals of <12 months or >60 months have an adverse effect on perinatal outcomes such as preterm birth, low birth weight, small for gestational age babies and congenital defects in babies (Dean, Lassi, Imam, & Bhutta, 2014b). While short pregnancy intervals <12 months are associated with anaemia, puerperal endometritis, premature rupture of membrane, longer intervals >60 months are associated with preeclampsia, third trimester bleeding and foetal death (Dean et al., 2014b). Furthermore the risks for folate and other nutritional deficiencies, cervical insufficiency, suboptimal breastfeeding, incomplete healing of uterine scar from previous caesarean delivery, and abnormal remodelling of endometrial blood vessels are higher for short interval and closely-spaced pregnancies (Conde-Agudelo et al., 2012). Therefore, it is important to intervene to delay the age of first pregnancy and optimise the intervals between the two pregnancies. There are numerous approaches that an intervention to promote birth spacing for women of reproductive age may undertake. Strategies may involve policies or population-based interventions, or a combination of school and community-based approaches (Aslam et al., 2015). Much like interventions focusing on delaying pregnancy, strategies that encourage women and couples to employ suitable spacing between births may involve health education, skills building and contraception education and distribution to ensure appropriate and consistent use of contraceptives (Aslam et al., 2015; Dean et al., 2014b). As per Aslam et al. (2015), these interventions may work by encouraging mothers to pursue educational avenues or work related accomplishments, in order to develop self-confidence, self-esteem and autonomy. A recent review on birth spacing interventions in low-, middle-, and high-income countries found studies with high quality evidence for a positive impact for repeat pregnancy/birth (Norton, Chandra-Mouli, & Lane, 2017). Successful interventions included those that targeted adolescents to teach them planning skills, including activities that involve preparing contraceptive plans. Folate plays an important role in protein synthesis and metabolism and other processes related to cell multiplication and tissue growth. Its deficiency during pregnancy causes megaloblastic anaemia and accumulates homocysteine in the serum which is associated with an increased risk in cardiovascular disease, late pregnancy complications such as preeclampsia, and NTDs around the time of conception (Lassi & Bhutta, 2012). The literature shows that iron supplementation during pregnancy can be a protective factor against low birth weight, and given alone or with folic acid it is effective in increasing iron stores and preventing anaemia during later gestation (Fernández-Gaxiola & De-Regil, 2011). Since women might not know when they become pregnant, it is therefore important to ensure iron and folic acid sufficiency from early life. Health promotion campaigns are a common strategy to increase a population's knowledge and awareness on the benefits and importance of nutritional supplementation. Two systematic reviews (Chivu, Tulchinsky, Soares-Weiser, Braunstein, & Brezis, 2008; Rofail, Colligs, Abetz, Lindemann, & Maguire, 2012) found that while these campaigns were successful in increasing overall awareness, knowledge, and consumption of folic acid before and during pregnancy, the increase in folic acid consumption was nowhere near optimal despite women having significantly increased knowledge. Interventions specific to adolescent nutrition are often conducted in school-based settings, one meta-analysis conducted by Salam et al. (2016) demonstrated that school-based delivery significantly reduced anaemia. While there is increasing evidence to support the provision of preconception care, the effectiveness of interventions to delay the age of first pregnancy, optimise birth intervals, and to provide periconception iron and folic acid supplement require further investigation. Determining the most effective delivery mechanisms across different settings is vital to successfully implementing pre- and peri-conception interventions in LMIC settings (Poels, Koster, Boeije, Franx, & van Stel, 2016). While there are existing reviews examining the effects of various interventions on preventing teen pregnancies (Dean et al., 2014b; Oringanje et al., 2009), they have mainly included randomised controlled trials (RCTs). In this review, we will also include evidence from large-scale programme evaluations in addition to relevant experimental studies, as randomisation is not always possible for all settings and populations. to ensure that review is and studies as and evidence for the included et al., 2013). These studies can systematic reviews by an intervention in different there are possible effects and can outcomes. did not review of interventions to optimise pregnancy intervals. reviews have pregnancy intervals from studies & et al., 2012; Dean et al., therefore it is important to review the evidence of interventions to interpregnancy intervals and their impact on maternal nutrition and birth outcomes. reviews have also the effects of periconception folic acid use (Dean et al., et al., 2015; et al., 2012) and acid use (Fernández-Gaxiola & De-Regil, these reviews are there is a to the evidence from and other large programme This review to the evidence on the effectiveness of preconception care interventions relating to delayed age at first pregnancy, optimising interpregnancy intervals, periconception folic acid, and periconception acid supplementation on maternal, pregnancy, birth, and child outcomes by the studies, with evaluations of existing This will a of the effectiveness of these interventions for maternal, birth and child health and nutrition outcomes. example, maternal outcomes for this review include pregnancy, anaemia, use of birth control knowledge and the risk of pregnancies and maternal and child health outcomes include mortality, the of neural tube defects and this review nutritional outcomes can be related to anaemia as well relating to folate such as blood cell folate or serum This evidence will be critical to and decision-making in LMICs. Interventions to delay age at first pregnancy. 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