Prevalence and determinants of gestational weight gain among pregnant women in Niger.

Abstract Low gestational weight gain (GWG) and low mid‐upper arm circumference (MUAC) are associated with adverse pregnancy outcomes. We aimed to assess the prevalence and determinants of low GWG and low MUAC among pregnant women in rural Zinder, Niger. A community‐based survey was conducted among 1,384 pregnant women in the catchment areas of 18 integrated health centers in the region of Zinder, Niger. Weight and MUAC were measured during an in‐home visit and again 1 month later, when haemoglobin concentration and micronutrient status were also assessed. The prevalence of low GWG was defined based on the 2009 United States Institute of Medicine (U.S. IOM) guidelines (<0.35 kg/week) and less than the third centile of the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH‐21st) standards. Factors associated with GWG and MUAC were identified using logistic regression models adjusting for season, village, and gestational age. The median (interquartile range) age was 25.0 (20.7, 30.0) years, and 16.4% were ≤19 years. The prevalence of low GWG were 62.9% and 27.5% according to 2009 IOM and less than the third INTERGROWTH‐21st centile, respectively; 24.9% had low MUAC. Higher α‐1‐acid glycoprotein (OR = 1.7, 95% CI [1.1, 2.8]) and C‐reactive protein (OR = 1.2, 95% CI [1.02, 1.50]) increased the odds of low GWG. Adolescents (OR = 2.7, 95% CI [1.8, 4.0]), housewives (OR = 1.97, 95% CI [1.36, 2.86]), and those who reported recent food assistance (OR = 1.80, 95% CI [1.04, 3.11]) had higher odds of low MUAC. Prevalence of low GWG and low MUAC was high among pregnant women. Determinants of GWG and MUAC included socio‐economic, demographic, and biological factors, although only markers of inflammation were consistent predictors across different definitions of low GWG.

In its 2009 guidelines, the U.S. Institute of Medicine (IOM) recommended a range for total GWG of 5 to 18 kg, with a GWG rate of 0.17 to 0.58 kg per week during the second and third trimesters (IOM and NRC, 2009). These guidelines of GWG are based on pre-pregnancy body mass index (BMI; IOM and NRC, 2009) and may only be relevant for women in the United States and other high-income countries. For low-income countries across the world, there has been limited information on recommended GWG, and the World Health Organization (WHO) does not currently have recommendations for GWG. However, the International Fetal and Newborn Growth Consortium for the 21st Century Project (INTERGROWTH-21st), which was implemented in eight countries, has recently published GWG standards based on gestational age (GA) in weeks (Cheikh Ismail et al., 2016).
These standards describe the GWG patterns of normal weight women at low risk of adverse maternal and perinatal outcomes and are intended to be applied globally.
Due to the lack of WHO GWG recommendations, and a shortage of basic supplies, including scales, in many health centers in lowincome countries, GWG monitoring is not a common practice in many parts of the world. Moreover, it has been shown that health workers lack adequate knowledge and skills to effectively monitor GWG (Goiburu, Alfonzo, Aranda, Riveros, & Ughelli, 2006;Mowe et al., 2006;Mowe et al., 2008). In Niger, the preterm birth rate and LBW prevalence are high, with 9.4 preterm births per 100 live births (Blencowe et al., 2012) and 27% of infants born LBW (UNICEF, 2017). In addition, the fertility rate of 7.4 children per woman is the highest in the world (UNICEF, 2017). However, information on pregnant women's nutritional status and GWG are limited. Thus, the objectives of the present study were to estimate the prevalence and the determinants of low GWG and low MUAC among pregnant women in Zinder, Niger.

| Study design and participants
The present study was a community-based survey conducted as part of the baseline assessment for the Niger Maternal Nutrition (NiMaNu) Project. This project was a programmatic intervention to improve antenatal care (ANC) services and compared pre-and post-intervention cohorts of pregnant women. Methods for the baseline survey assessments have been described in detail elsewhere (K. Begum et al., 2018;Wessells et al., 2017). Briefly, the community-based baseline survey was conducted from March 2014 to September 2015.
We enrolled pregnant women in 68 rural villages belonging to 18 integrated health centers (IHCs) in the catchment area of two health districts (Mirriah and Zinder), in the Zinder region, Niger. The 18 IHCs were selected based on their accessibility and their distance to Zinder, the regional capital, and because of the limited number and scope of interventions that were being implemented in their catchment area. Within the catchment area of each IHC, the village containing the IHC was automatically included in the survey, as well as one additional randomly selected village among those with a health post. Among the remaining villages in the catchment area of each

Key messages
• GWG and MUAC are strong predictors of birth outcomes. In low-income countries, information on GWG and MUAC is limited.
• There was a high prevalence of low GWG and low MUAC among pregnant women in rural Zinder, Niger.
• Determinants of GWG and MUAC included socioeconomic, demographic, and biological factors, particularly markers of inflammation.
• Considering the importance of adequate GWG and MUAC for maternal health and pregnancy outcomes, effective and cost-effective interventions to ensure adequate GWG and nutritional status are needed.
IHC, four villages ≤10 km and four villages >10 km were randomly selected and randomized to order of participation. Pregnant women from the first two selected villages (IHC-village and health post village), and the first two villages from the subsequent randomization   were enrolled, with a target of enrolling approximately 16-20 women   per village and a sample size of approximately 77 women per IHC. When the target number of women was not met by the first four villages in each IHC, women were included from the remaining villages of each IHC following the order of the randomization list. Within each village, participants were identified using a random walk method (United Nations, 2008).
The enrolment of participants was implemented continuously over a period of 18 months with approximatively one new IHC surveyed each month. All identified pregnant women (regardless of gestational week) were eligible for study participation, if they had resided in a participating village for at least 6 months prior to enrolment and had no plans to move out of the study area within the next 2 months. A woman was excluded if she had a severe illness warranting immediate hospital referral or was unable to provide consent due to impaired decision-making ability.

| Data collection and outcomes
Each enrolled woman participated in two study visits. During the first contact (Visit 1), we obtained written informed consent and interviewed women using a structured questionnaire to collect information regarding SES, demographics, and knowledge, attitude, and practices relating to diet, health, pregnancy (current and previous), and ANC attendance. Pregnant women were weighed in light clothing in duplicate to 50-g precision (SECA 874). Women's height (SECA 213, Seca, Hamburg, Germany), MUAC (ShorrTape© Measuring Tape), and symphysis-fundal height (ShorrTape© Measuring Tape, Weigh and Measure, Olney, MD) were measured in duplicate to 0.1-cm precision.
A third measurement was performed, and the mean of the two closest measurements was calculated when the first two measurements were >0.2 kg (weight) or >0.5 cm apart (height, MUAC, and symphysisfundal height).
GA was estimated as a weighted average of the following obtained information: reported last menstrual period (by estimated number of months, lunar cycles, and/or proximity to a religious or cultural event), time elapsed since quickening, and two fundal height measurements taken approximately 1 month apart (Hess & Ouedraogo, 2016). Three proxy indices (housing quality, household assets, and household livestock) were used to estimate the household SES, as previously described (K. Begum et al., 2018). Household food insecurity was assessed using the Household Food Insecurity Access categories (Coates, Swindale, & Bilinsky, 2007). Pregnant women's dietary practices were assessed using a list-based food frequency questionnaire, and those who reported consuming at least five of 10 defined food groups in the previous 24 hr were considered to meet the Minimum Dietary Diversity for Women (FAO and FHI 360, 2016).
The outcomes of this study included GWG per week (in kilograms), low GWG, MUAC (in centimeters), and low MUAC. GWG per week was calculated by subtracting weight at Visit 1 from the weight recorded on Visit 2 divided by the number of elapsed days and multiplied by seven. Adequacy of GWG was assessed by comparing GWG of the study participants with the 2009 U.S. IOM guidelines for GWG and the INTERGROWTH-21st standards, as described in more detail below. Low MUAC was defined as <23 cm (Ververs et al., 2013).

| GWG compared with the 2009 U.S. IOM guidelines for GWG
The mean GWG recommended by the U.S. IOM is 0.45 kg/week, with ranges from 0.44 to 0.58 kg/week for underweight and 0.35 to 0.50 kg/week for normal weight women, respectively (IOM and NRC, 2009). These guidelines are based on pre-pregnancy BMI, which are not known for the participants in the present study. Thus, considering that the majority of women in the present study were likely to be either underweight or of normal weight (Institut National de la Statistique & ICF International, 2007), a GWG of 0.35-0.58 kg/week was considered within the IOM guidelines. Less than 0.35 kg/week was considered as GWG below the IOM guidelines (or a proxy for low GWG) and >0.58 kg/week as GWG above the IOM guidelines (or a proxy of excessive GWG). Because the IOM guidelines apply to women in the second and third trimester of gestation, women in their first trimester of pregnancy were excluded from this classification.
Considering that the majority of women had low or adequate GWG in the present study population, GWG was transformed in a dichotomous variable (i.e., GWG < 0.35 kg and GWG ≥ 0.35 kg) to assess factors associated with low GWG.

| GWG compared with the INTERGROWTH-21st standards
We calculated the observed GWG per week for each pregnant woman according to her estimated GA in weeks. Because the published INTERGROWTH-21st standards represent cumulative GWG, they cannot be directly compared with the observed GWG per week.
Rather, the observed GWG was compared with the GWG rate per Observed GWG less than the third centile of the GWG by GA of the INTERGROWTH-21st standards was considered to be GWG below the INTERGROWTH-21st standards (or a proxy for low GWG).
Observed GWG between the third and the 97th centile was considered GWG within the standards (or a proxy of normal weight gain), and observed GWG > 97th centile of expected GWG was considered GWG above the INTERGROWTH-21st standards (or a proxy of excessive GWG). Observed GWG per week of the participants was also compared with the median of the INTERGROWTH-21st standards and categorically defined as being above or below the INTER-GROWTH-21st median.

| Sample size
The overall sample size for the NiMaNu project was specified to be able to detect with 80% power a difference of 10% in the prevalence of anaemia as the primary outcome of the programmatic intervention (Hess & Ouedraogo, 2016). Assuming an initial anaemia prevalence of 50%, a significance level of 0.05, power of 0.80, and a design effect of 2 to account for the cluster sampling design, a sample size of 768 was needed, which was then inflated by 17% for attrition, yielding a target sample size of 925 pregnant women for the baseline survey. However, for the impact assessment of the main trial described elsewhere (Hess & Ouedraogo, 2016), the baseline survey was extended for 6 months to allow statistical models to account for the potential seasonal effects of participants' enrolment on the outcome measures. Based on the same assumption as above, the additional sample size required for the baseline survey was estimated at 77 pregnant women per month for a total of 463 over 6 months. In total, 1,388 pregnant women were needed to be enrolled in the baseline survey to provide 80% power to detect a difference of 10% in the prevalence of anaemia in the primary impact assessment. Data were successfully obtained from 1,385 pregnant women. This sample size was adequate to estimate the prevalence of low GWG + 3.5% (95% CI), assuming a prevalence of 50%.

| Statistical analysis
Data were double-entered and compared using EpiData Entry version 3.1 (Odense, Denmark). All statistical analyses were performed using the SAS System version 9.4 (SAS Institute, Cary, NC, USA). We analysed available data from the baseline survey of the NiMaNu project. Data were examined using univariate analysis (graphical plotting) to look for outliers. Outliers that were clearly impossible or implausible values were corrected if possible, or trimmed when correction was not possible, which was the case for one GWG and one MUAC measurement. A detailed statistical analyses plan is available (Hess & Ouedraogo, 2016).
GWG per week and MUAC were assessed for conformance to the normal distribution. Predictors not normally distributed (i.e., ferritin, sTfR, CRP, AGP, and folate and vitamin B 12 ) were natural log transformed. Descriptive analysis of initial characteristics of study participants was performed. Factors associated with low GWG and low MUAC, as well as GWG per week and MUAC as continuous variables, were identified using generalized estimating equation models, in SAS proc glimmix to permit adjusting for cluster effects by village. All models were minimally adjusted to include year, season, and village, and analyses were performed using robust standard errors. All predictors were run in individual models, and the minimally adjusted odds ratio (for low GWG and MUAC as binary outcomes) and the minimally adjusted mean difference (for GWG and MUAC as continuous outcomes) from each individual model were reported.
Potential predictors were identified based on a literature review and background knowledge and prespecified in the statistical analyses plan (Hess & Ouedraogo, 2016). These included maternal age, education, number of pregnancies, number of living children, height, occupation, SES, household food insecurity, reported increase or decrease in the number of meals per day and quantity of food consumed due to pregnancy, reported receipt of food assistance, adequate minimum dietary diversity, micronutrient status (plasma ferritin, zinc, and retinol binding protein adjusted for inflammation; Wessells et al., 2017;sTfR, vitamin B 12 , and folate), markers of inflammation (AGP and CRP), and malaria antigenemia (HRP2). To explore which predictors were consistently and significantly associated with GWG per week and low GWG, we ran five independent analyses including GWG per week and GWG < 0.35 kg/week adjusting for women's GA, and GWG per week, GWG less than the third centile and GWG < 50th centile INTERGROWTH-21st standards not adjusting for GA following the methods of the respective standards (Cheikh Ismail et al., 2016;Hutcheon & Bodnar, 2018;IOM and NRC, 2009). If a predictor was associated with at least three GWG (GWG per week and/or different definitions of low GWG) or both of the MUAC outcomes (MUAC in centimeters or low MUAC), it was considered to be a consistent predictor of low GWG or undernutrition. A P value <.05 was considered as statistically significant for the all tests performed.

| Ethics
This study was part of the NiMaNu Project, which was approved by the National Ethical Committee in Niamey (Niger) and the Institutional Review Boards of the University of California, Davis (USA). The study was registered at www.clinicaltrials.gov as NCT01832688. In the presence of a neutral witness, consent materials were presented in both written and oral formats. Informed consent was obtained and documented with a written signature or a fingerprint.

| Characteristics of study population
A total of 1,385 pregnant women were enrolled during the baseline survey, and 67.9 % (n = 940) completed Visit 2 (Figure 1), with 81.9 % (n = 770) of these women assessed for micronutrient status. Attrition at Visit 2 was due to birth, relocation, consent withdrawal, stillbirth, and maternal death. The mean participants' age was 26.2 ± 6.4 years, and only 20.9% had attended any formal schooling. The majority of the participants considered themselves to be primarily housewives (83.2%), and 53.1% were in their third trimester of gestation (Table 1). Of the 1,385 pregnant women interviewed, 39.5% of women had attended at least four ANC during their last pregnancy as described in Table 1. GWG analyses included all pregnant women who completed follow-up Visit 2 and were in the second and third trimester of pregnancy (n = 917); 1,384 women enrolled at Visit 1 were included in the MUAC analyses. Using the U.S. IOM 2009 guidelines and the INTER-GROWTH-21st standards, the prevalence of low GWG was 62.9% and 27.5%, respectively (Table 2). In contrast, 13.1% and 2.0% of pregnant women were above the 2009 IOM guidelines and above the 97th centile of the INTERGROWTH-21st standards, respectively, indicating excessive GWG ( Figure S1, Table 2). The median MUAC was 24.1 (interquartile range 18.0, 36.9) cm, and 24.9% had low MUAC (Table 2).

| Determinants of GWG per week and low GWG among pregnant women
Analyses performed using the minimally adjusted models indicated that two predictors were consistently and significantly associated with both GWG per week and low GWG, as defined by both U.S. IOM guidelines and INTERGROWTH-21st standards (Table 3), and some predictors were significant in individual models.

| DISCUSSION
The prevalence of low GWG was high among pregnant women in Zinder irrespective of whether the IOM guidelines or the INTER-GROWTH-21st standards were used. More than one in two pregnant  Ethiopia, the prevalence of low GWG based on the total GWG according to the IOM criteria was also high (69.3%; Asefa & Nemomsa, 2016). Given the adverse maternal and child health outcomes associated with low GWG, our findings indicate that low GWG is a concern in the study area and highlights the need for effective maternal health and nutrition interventions to influence these outcomes (Hamad, Cohen, & Rehkopf, 2016).
The two sets of cut-offs used for GWG in the present study differ substantially. For example at 28 weeks of GA, the IOM cutoff for low GWG is 0.35 kg/week, and the third centile of the INTERGROWTH-21st standard is 0.27 kg/week. Consequently, we found that the prevalence of low GWG according to the 2009 U.S. IOM guideline (GWG <0.35 kg/week) was about two times higher than the prevalence based on the third centile of the INTERGROWTH-21st standards.
The IOM guidelines were developed based on the available published literature as well as the reports of consultants, and the goal was to identify GWG values or range of GWG values in the U.S. population associated with lowest prevalence of adverse outcomes including caesarean delivery, postpartum weight retention, preterm birth, small-or large-for-GA birth, and childhood obesity (IOM and NRC, 2009). Conversely, the INTERGROWTH-21st standards are derived from a prospective longitudinal, multicountry population study. They represent GWG of healthy, well-nourished, and educated women who had a BMI between 18.5 and 24.9 in the first trimester of pregnancy with good maternal and perinatal outcomes (Cheikh Ismail et al., 2016).
Interestingly, the INTERGROWTH project did not find any countryspecific differences, suggesting that these standards may be useful internationally. However, the third centile of the INTERGROWTH-21st standards identifies women with severely low GWG as compared with the IOM guidelines, and using another, slightly higher centile may be more useful for identifying women at risk of low GWG.
In the present study, we were also interested in assessing the prevalence of low MUAC as another indicator of nutritional status during pregnancy, because MUAC reflects both past and current nutritional status (WHO expert Committee on physical status, 1995). We found that a significant proportion of pregnant women had low MUAC. In a study conducted in Ethiopia, a similar prevalence of low MUAC (31.8%) was reported among pregnant women (Mariyam & Dibaba, 2018), although this study applied a cutoff of 21 cm.
Our study revealed that higher concentrations of markers of systemic inflammation (AGP and CRP) and higher concentrations of sTfR (indicative of iron deficiency and/or increased erythropoiesis) were associated with decreased GWG per week and increased odds of low GWG. Inflammation and iron deficiency can be accompanied by loss of appetite, decreasing food intake, and possibly leading to low weight gain during pregnancy (Katona & Katona-Apte, 2008;Raiten et al., 2015;Scrimshaw, 1977). However, it is interesting to note that higher plasma ferritins concentrations (indicative of iron sufficiency and/or inflammation) were associated with increased odds of GWG less than the third centile of INTERGROWTH. Although ferritin concentrations were adjusted for inflammation in the present study, it is possible that adjustments did not fully capture the effects of inflammation.
We found that taller women had lower odds of low GWG and lower odds of low MUAC. Similar findings were reported in the Philippines, where higher maternal height was associated with greater total     Increased gravidity was associated with increased odds of low GWG (<50th centile); similar findings have been reported in Tanzania (Changamire et al., 2014). It is possible that higher gravidity and parity, and frequent reproductive cycling, may result in maternal nutritional depletion in the context of high food insecurity and thus increasing the risk of SGA and LBW (Klerman, Cliver, & Goldenberg, 1998;Miller, 1991 were not available in the present study. In addition, the INTER-GROWTH-21st standards are derived from healthy, well-nourished, and educated women, and participants had normal BMI in the first trimester of pregnancy (Cheikh Ismail et al., 2016). Thus, it is likely that some women in the present study were misclassified according to the IOM guidelines and the INTERGROWTH-21st standards. Nevertheless, by using both sets of cutoffs and running analyses with multiple definitions of low GWG, we were likely able to identify women at highest risk of low GWG and explore risk factors associated with low GWG. Lastly, a significant proportion of pregnant women in the study population (16.3%) were adolescent, but due to the lack of a specific MUAC recommendation for the adolescent age group, those women were classified using the same guidelines and standards as adult women. For GWG, the IOM did not see sufficient evidence to support a specific guideline for adolescents (IOM and NRC, 2009). Similarly, we did not find a higher risk of low GWG among adolescent in the present study, but further research is needed (Harper, Chang, & Macones, 2011).

CONFLICTS OF INTEREST
The authors declare that they have no conflicts of interest.

CONTRIBUTIONS
The NiMaNu Project was conceived and designed by SYH, KRW, and CTO. Data were analysed by CTO with the guidance from RRY and SYH. Results were interpreted by all co-authors. CTO drafted the manuscript, and SYH edited the manuscript. All authors reviewed and approved the final version of the manuscript.