Journal of Perinatology (2014) 34, 351–356 & 2014 Nature America, Inc. All rights reserved 0743-8346/14 www.nature.com/jp
ORIGINAL ARTICLE
Prediction of excessive gestational weight gain from week-specific cutoff values: a cohort study J Knabl1,5, C Riedel2,5, J Gmach1,2,3,4, R Ensenauer3, L Brandlhuber3, KM Rasmussen4, B Schiessl1 and R von Kries1,2 OBJECTIVE: To assess the prognostic validity of the Institute of Medicine/National Research Council (IOM/NRC) week-specific cutoff values for inadequate or excessive total gestational weight gain (GWG) by 4-week intervals. STUDY DESIGN: We merged data from two German cohorts (LMU cohort (all maternal-weight categories) and PEACHES cohort (obese women)) to provide information on GWG for 749 women (365 normal weight, 199 overweight and 185 obese). We calculated the prognostic values for suboptimal and excessive GWG according to the IOM/NRC cutoff values. RESULT: The positive predictive values for excessive total GWG for those who experienced excessive GWG early in pregnancy was 70.1% (95% confidence interval (CI) 60.5; 78.6) as of week 12/1 to 16/0 in normal-weight women, 89.5% (95% CI 75.2; 97.1) and 95.2 (76.2; 99.9) 95.2% (95% CI 76.2; 99.9) as of week 8/1 to 12/0 for overweight and obese women, respectively. In absence of excessive GWG as of week 12/1 to 16/0, normal-weight women had 77.5% (95% CI 77.1; 83.1) probability of not experiencing excessive total GWG (negative predictive value). In overweight and obese women, the negative predictive value was considerably lower up to week 24/1 to 28/0 (60.0% (95% CI 48.8; 70.5) in week 20/1 to 24/0 and 50.6% (95% CI 39.3; 61.9) in week 24/1 to 28/0). Most women with inadequate GWG in the first and second trimester had adequate total final GWG (positive predictive value for total inadequate GWG o50% up to week 16/1 to 20/0 in all groups). CONCLUSION: As women with excessive weight gain can be identified with high confidence if the GWG exceeds the IOM/NRC week-specific cutoff values, interventions may be initiated early in pregnancy. Journal of Perinatology (2014) 34, 351–356; doi:10.1038/jp.2014.22; published online 27 February 2014 Keywords: pregnancy; excessive weight gain; gestational weight gain; prediction; cohort study
INTRODUCTION Measuring gestational weight gain (GWG) is traditionally part of prenatal care. Current GWG guidelines of the Institute of Medicine (IOM)/National Research Council (NRC) emphasize the importance of adequate weight gain during pregnancy and include weekspecific cutoff values for adequate GWG1 because GWG is an important determinant for fetal and maternal outcomes.2–5 Evidence for the association of inadequate and excessive GWG with maternal and fetal pregnancy outcome is based on total GWG, which can only be determined at term.2–5 Recent metaanalyses have shown that interventions, such as increasing physical activity or nutritional counseling, may assist women to increase or reduce total GWG.6–8 Although some prediction of the risk for excessive total GWG is possible based on the a priori population risk for excessive total GWG, which increases by the body mass index (BMI) category, these a priori risks do not allow for individual counseling and targeted interventions. Individual risks identified early in pregnancy and specific counseling is likely to account for a higher motivation to limit weight gain in the respective mothers than a general statement. Therefore, women at risk of gaining outside the recommended ranges should be identified early in pregnancy so possible interventions can occur. The trimester-specific cutoff
values provided by the IOM/NRC guidelines1 allow identification of women with such outlying GWG values. For counseling of pregnant women one must know the predictive value of these outliers to identify pregnancies at risk for excessive or inadequate total GWG. We previously demonstrated that some prediction of total GWG is possible by trimesterspecific cutoff values.9 For counseling mothers, however, there is a need to strive for more precise prediction. This can be achieved by assessment of the predictive value of week-specific cutoff values. Predictions with tighter intervals are required. The objective of our study was to assess the prognostic validity of the week-specific IOM/NRC cutoff values to predict inadequate or excessive total GWG by 4-week intervals. METHODS We aimed for a precision of ±10% in the predictive values of early GWG in normal-weight, overweight and obese mothers. For predictive values of X75%, this requires 120 women for each maternal-weight category. To allow for a safety margin in case of lower estimates, we aimed to include at least 150 women in each BMI category. We used a three-step strategy to accomplish this. First, between 9 December 2010 and 31 October 2011, 2270 consecutive deliveries, in the Department of Obstetrics and Gynecology of the Ludwig-Maximilians-University
1 Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universita¨t Mu¨nchen, Munich, Germany; 2Division of Epidemiology, Institute of Social Paediatrics and Adolescent Medicine, Ludwig-Maximilians-Universita¨t Mu¨nchen, Munich, Germany; 3Research Center, Dr von Hauner Children’s Hospital, Ludwig-Maximilians-Universita¨t Mu¨nchen, Munich, Germany and 4Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA. Correspondence: Professor R von Kries, Departement of Epidemiology, Institute of Social Paediatrics and Adolescent Medicine, Ludwig-Maximilians-Universita¨t Mu¨nchen, Heiglhofstr. 63, Munich 81377, Germany. E-mail: [email protected] 5 These authors contributed equally to this work. Received 25 September 2013; revised 10 December 2013; accepted 13 January 2014; published online 27 February 2014
Early prediction of excessive GWG J Knabl et al
352 Table 1.
Sample description
Characteristics
Maternal age (years) Height (cm) Prepregnancy weight (kg) BMI categoryd Underweight Normal weight Overweight Obese Birth weight of the child (g) Gestational age (weeks)
Deliveries eligible but not available for the study population (LMU cohortc) n ¼ 977 Mean (s.d.)/ % (n)
Deliveries available for the study population (LMU cohortc) n ¼ 1423 Mean (s.d.)/ % (n)
Deliveries available for the study population (PEACHES cohort) n ¼ 147 Mean (s.d.)/ % (n)
33.1 (5.1) 168.1 (6.6) 63.2 (10.0)
32.2 (5.5)a 167.2 (6.7)a 65.4 (12.6)a
30.6 (5.0)b 168.2 (6.8)b 103.3 (16.6)b
(51) (732) (103) (38)
5.8 (79)a 65.2 (891)a 21.6 (295)a 7.5 (102)a
— — 4.1% (6)b 95.9% (141)b
3193 (714) 38.4 (2.9)
3302 (597)a 39.0 (2.2)a
3488 (474)b 40.1 (1.5)b
5.5 79.2 11.1 4.1
Abbreviations: BMI, body mass index; LMU, Ludwig-Maximilians-University; PEACHES, Programming of Enhanced Adiposity Risk in CHildhood—Early Screening cohort. a Significantly (Po0.05) different from deliveries eligible but were not included in the study population. b Significantly (Po0.05) different from deliveries available for the study population (LMU cohort). c Women who delivered in the Department of Obstetrics and Gynecology of LMU Munich between December 2010 and October 2011, and overweight/obese women who delivered between November 2011 and September 2012. d Differences in number of cases to overall number of cases (977 and 1423) are because of missing values of height and pregregnancy weight in women from the LMU cohort.
Munich (University of Munich, LMU), were considered. During the hospital stay, a research assistant abstracted these mothers’ records on weight gain on most days (except for weekends and holidays). This step allowed recruiting sufficient normal-weight mothers. Second, inasmuch as the proportion of overweight and obese mothers recruited was small, we oversampled overweight and obese mothers in the LMU cohort. The research assistant contacted overweight (BMIX25 and o30 kg m 2) and obese mothers (BMIX30 kg m 2) who had delivered on days when she had not been in hospital by telephone and as well as overweight and obese mothers who delivered between November 2011 and September 2012. She asked both groups of LMU mothers to read the weight-gain values from their pregnancy records. As a result, the LMU cohort included information on GWG for 2400 deliveries. Third, inasmuch as the number of obese mothers was still below our target sample size, we also included obese women who delivered in other hospitals in the catchment area as for the LMU cohort (n ¼ 147 (6 overweight and 141 obese)) from an ongoing observational study on pregnancy outcomes in obese women PEACHES (Programming of Enhanced Adiposity Risk in CHildhood—Early Screening cohort)10,11 in our analysis. This observational prospective study required active involvement of the obese mothers, so only those who volunteered to follow-up visits were included (Table 1). To achieve a homogenous population for analysis, we excluded women who had multiple births, preterm delivery, diagnosis of diabetes mellitus or gestational diabetes mellitus or with missing information on prepregnancy weight, the date of last weight measurement during pregnancy before the 37th week of pregnancy (36/0 week) (Figure 1). We also excluded underweight women because the prevalence of underweight in these birth cohorts was too low for our planned analyses.12,13 Weight-gain values below the 0.1% percentile or above the 99.9% percentile in each gestational month and weight measurements after the 42nd week of pregnancy were defined as implausible and were excluded from analyses (Figure 1). Data on weight gain during pregnancy were read from the ‘maternity notes’, either by the research assistant or by the mother during a telephone interview with the research assistant. In Germany, ‘maternity notes’ are issued to every pregnant woman at her first antenatal visit to the obstetrician. The ‘maternity notes’ include complete documentation of health-care visits during pregnancy. They are an identical copy of all important pregnancyrelated medical records that the patient carries with her for hospital stays or emergencies. Written informed consent was obtained in PEACHES but was not required in the LMU cohort, as this is an anonymous analysis of routine data. The retrospective evaluation of regular medical records was approved by the ethics committee of the LMU Munich, Germany. Total GWG was defined as the difference between a woman’s selfreported prepregnancy weight and the last weight measured before delivery. According to the IOM/NRC guidelines, adequate total GWG was classified as total gain of 12.5 to 18 kg for underweight women, 11.5 to 16 kg for normal-weight women, 7 to 11.5 kg for overweight women and Journal of Perinatology (2014), 351 – 356
5 to 9 kg for obese women.1 Inadequate GWG was defined as GWG values below the recommended GWG and excessive GWG as values above the recommended GWG. The required information on maternal prepregnancy weight and of weight measurement during pregnancy was gathered from the ‘maternity notes’. One gestational interval was defined as 4 weeks, for example, interval 2 was defined as pregnancy week 4/1 days to week 8/0 days. We divided pregnancy into ten 4-week intervals. For example, interval 10 includes the time period from 36 completed gestational weeks and 1 day (36/1 weeks) to 40 completed gestational weeks and 0 days (40/0 weeks). Cutoff points for inadequate and excessive GWG were calculated for each week according to the IOM/NRC guidelines. In these guidelines, GWG increases linearly with different slopes in the first trimester (weeks 1 to 13) and the following two trimesters (weeks 14 to 40).1 Compared with the second and third trimesters, the increments of GWG in the first trimester are smaller. For normal-weight women, for example, the upper cutoff point of adequate GWG in the first trimester is 3 kg. After subtracting from the upper cutoff point of total GWG (16 kg) at the end of pregnancy, the upper limit in the remaining 27 weeks is a total of 13 kg. This results in a weekly gain of 0.23 kg in the first trimester and 0.48 kg in the second and third trimesters. Similarly, the lower cutoff point in the first trimester for normalweight women is 1 kg. Subtracted from the lower cutoff point of total GWG (11.5 kg), the lower limit in the remaining 27 weeks is a total of 10.5 kg. This results in a weekly gain of 0.08 kg in the first trimester and 0.39 kg in the second and third trimesters. To obtain the numeric IOM/NRC upper and lower limits of weight gain for every week, we accumulated the weekly gains according to the underlying formula. For example, in week 18/0 the upper limit was 5.4 kg (3 kg in the first trimester plus 5 weeks 0.48 kg per week) and the lower limit was 2.95 kg (1 kg in the first trimester plus 5 weeks 0.39 kg per week) for normal-weight women. For each woman, we compared her actual cumulative GWG up to the particular week for which data were available in the respective 4-week interval and assessed whether her gain was adequate or below or above the week-specific cutoff points (yes or no). Inasmuch as there are different recommendations for each maternal prepregnancy BMI category, this procedure was conducted separately for each one. BMI was calculated by dividing weight in kilograms by squared height in meters. Categories of BMI were defined according to the IOM/ NRC guidelines and the World Health Organization (WHO) criterion.14 We used t-tests for numeric and Fisher’s exact test for categorical data for comparisons of the characteristics of the subjects. We calculated prognostic values for inadequate and excessive GWG for each gestational interval starting with interval week 4/1 to 8/0 because there were very few observations before 4/1 weeks. The respective interval-specific positive predictive values (PPV) and negative predictive values (NPV) and the positive likelihood ratio (LR þ ) and negative likelihood ratio (LR ) were determined. The PPV’s indicate the proportion & 2014 Nature America, Inc.
Early prediction of excessive GWG J Knabl et al
353
Figure 1.
Flow charts of sample size.
of the individuals exposed to excessive or inadequate GWG early in pregnancy who will experience excessive or inadequate GWG, respectively, at delivery. The NPV’s indicate the proportion of the individuals with absence of excessive or inadequate GWG early in pregnancy who will not experience excessive or inadequate GWG, respectively, at delivery. The likelihood ratios (LR) provide a basis to calculate the post-test probabilities for excessive or inadequate total GWG for exceeding week-specific IOM cutoff values (LR þ : for test positives; LR : for test negatives). Exact binomial 95% CI were calculated for PPV and NPV.15 All statistical analyses were conducted using the public domain statistical software R 2.14.2 (ref. 16) (http://cran.r-project.org), with the package epiR.17
RESULTS In the LMU cohort 2400 women were eligible; 1423 of these and the 147 women in the PEACHES cohort provided information on GWG. The application of the exclusion criteria reduced the number of women available for the final analysis to 749 (Figure 1). In the final study population the proportion of pregnancies with excessive total GWG increased with increasing BMI category (38.8%, 64.7% and 65.1% for normal-weight, overweight and obese mothers, respectively). The proportion of pregnancies with inadequate GWG was 18.9% in normal-weight, 6.9% in overweight and 12.9% in obese mothers. There were significant differences between the women from the LMU cohort who were eligible but not available for the study & 2014 Nature America, Inc.
and those from the LMU cohort who were available and provided information (Table 1), reflecting oversampling of overweight and obese women accounting for slightly younger and shorter and heavier mothers and slightly heavier children in the final study population. Prognostic value of the upper cutoff values to predict excessive GWG The PPV indicates the probability for excessive total GWG conditional on exceeding the week-specific IOM/NRC cutoff value by defined 4-week time intervals. For normal-weight mothers, the PPV for excessive total GWG increased continuously from the gestational week 16/0 to week 40/0. PPVs above 70.1% (95% CI 60.5; 78.6) were reached as of week 12/1 to 16/0 (Table 2). This is also reflected in increasing LR þ values. In overweight and obese mothers, the PPV was higher almost throughout pregnancy reaching values above about 89.5% (95% CI 75.2; 97.1) and 95.2% (95% CI 76.2; 99.9) as of week 8/1 to 12/0 (Tables 3 and 4). The prediction for absence of excessive GWG (NPV) at the end of pregnancy from GWG within the IOM/NRC ranges was at or above 77.5% (95% CI 77.1; 83.1) as of the interval week 12/1 to 16/0 in normal-weight women (Table 2), but only exceeded 50% in week 24/1 to 28/0 (60.0% (95% CI 48.8; 70.5) and 20/1 to 24/0 (50.6 % (95% CI 39.4; 61.8) in overweight and obese women, respectively (Tables 3 and 4). Journal of Perinatology (2014), 351 – 356
Early prediction of excessive GWG J Knabl et al
354 Table 2. Positive predictive values, negative predictive values, positive and negative likelihood ratios of the week-specific Institute of Medicine/ National Research Council GWG cutoff values for excessive and inadequate GWG in normal-weight women Excessive GWG Positive predictive value (%) (95% CI) Week Week Week Week Week Week Week Week Week
4/1–8/0 8/1–12/0 12/1–16/0 16/1–20/0 20/1–24/0 24/1–28/0 28/1–32/0 32/1–36/0 36/1–40/0
62.1 61.6 70.1 69.4 73.0 77.2 80.4 81.0 87.6
(48.4; (51.3; (60.5; (59.9; (64.2; (69.2; (73.0; (74.0; (81.3;
74.5) 71.2) 78.6) 77.8) 80.6) 84.0) 86.6) 86.8) 92.4)
Inadequate GWG
Positive likelihood ratio
Negative predictive value (%) (95% CI)
Negative likelihood ratio
Positive predictive value (%) (95% CI)
Positive likelihood ratio
Negative predictive value (%) (95% CI)
Negative likelihood ratio
2.67 2.58 3.65 3.58 4.22 5.30 6.44 6.70 11.20
73.6 (64.8; 81.2) 72.5 (66.0; 78.4) 77.5 (77.1; 83.1) 77.9 (71.9; 83.4) 82.1 (76.1; 87.2) 88.8 (83.3; 92.9) 90.5 (85.6; 94.2) 94.1 (89.9; 96.9) 96.7 (93.3; 98.7)
0.59 0.61 0.45 0.45 0.34 0.20 0.16 0.10 0.05
32.1 (21.9; 43.6) 38.0 (28.8; 47.8) 52.8 (40.7; 64.7) 46.9 (35.7; 58.3) 63.2 (50.7; 74.6) 74.1 (60.3; 85.0) 80.0 (67.7; 89.2) 83.6 (71.2; 92.2) 95.0 (86.1; 99.0)
2.01 2.50 4.70 3.92 7.10 11.79 17.17 21.95 81.51
91.1 (83.8; 95.8) 90.1 (85.1; 93.8) 91.1 (86.7; 94.4) 91.5 (87.1; 94.7) 92.4 (88.4; 95.4) 91.4 (87.4; 94.5) 94.0 (90.6; 96.5) 92.8 (89.3; 95.3) 96.1 (93.2; 98.0)
0.42 0.45 0.41 0.41 0.34 0.39 0.27 0.33 0.18
Abbreviations: CI, confidence interval; GWG, gestational weight gain.
Prognostic value of the lower cutoff values to predict inadequate GWG Inadequate GWG in the first and second trimester of pregnancy was a poor predictor for total inadequate GWG irrespective of maternal prepregnancy BMI category. Conversely, inadequate total GWG was unlikely if GWG was within the recommended ranges early in pregnancy (Tables 2–4).
DISCUSSION We found that women with normal GWG in early pregnancy were unlikely to experience inadequate GWG, but could still gain above the GWG guidelines. Women with excessive GWG early in pregnancy were highly likely to develop excessive total GWG and may benefit from an intervention to help them to gain within the guidelines. In contrast, women with inadequate GWG early in pregnancy had a fair chance to gain within the GWG guidelines without specific intervention. Our data allow for precise and early identification of women at risk for excessive GWG, a prerequisite for counseling and implementation of targeted interventions. To our knowledge, there is only one study on the prognostic value for exceeding IOM/NRC recommendations early in pregnancy. This study was based on prediction by trimester only.9 The reported trimester-specific predictive values might be overestimates because of methodological limitations of the study.9 Here, we had adequate numbers of women in all studied maternal prepregnancy BMI categories to develop PPVs with high precision, which allows physicians to counsel their patients with confidence. Women who are at risk for excessive or inadequate GWG must be identified so as to assign them to the appropriate intervention. The importance of risk-guided counseling for excessive and inadequate GWG has recently been outlined.18 Targeted interventions are mandatory. According to the largest meta-analysis to date,6 reducing GWG is not beneficial for all pregnant women, and would be harmful for those with suboptimal GWG or weight loss.7,18 In our study, prediction of inadequate total GWG from inadequate GWG early in pregnancy was poor, so targeted interventions to increase GWG in such pregnancies may not appear justified in affluent countries as Germany. This may not be the case in poorer countries.19 In contrast, excessive GWG early in pregnancy—especially for overweight and obese women—is a good predictor of excessive total GWG and should prompt interventions. This is especially important because early excessive GWG is rarely reversible without special interventions.20 According to a recent Journal of Perinatology (2014), 351 – 356
meta-analysis,5 interventions to limit excessive GWG are likely to be effective and might also reduce the risk for poor pregnancy outcomes and later overweight of the child. In a recent observational study, reversal from excessive GWG in the first two trimesters to normal in the third trimester was associated with a reversal of the risk for childhood overweight related to excessive GWG.21 Therefore interventions to avoid excessive GWG in mothers at risk of excessive GWG appear warranted. The key elements of such interventions are weight monitoring, increasing physical activity and dietary counseling, as observed in some meta-analyses.4,6 Our study population had the major advantage of a sufficient number of weight measurements for each woman in the relevant maternal BMI categories. The major strength of our findings is their high precision for prediction of excessive GWG from early GWG in all maternal-weight categories. All data for this study were obtained from medical records. All weight data apart from prepregnancy weight, which was recalled at the time of the first antenatal visit, were measured. This is important because self-recall of weight during pregnancy may cause misclassification of GWG,22 whereas recall of prepregnancy weight seems to be more reliable.23 Underestimation of selfreported prepregnancy weight and, therefore, overestimation of GWG (as shown elsewhere24) appears unlikely in our data, however, because of a close correlation of the reported prepregnancy weight and the first weight measured in pregnancy, which approximated the expected mean weight gain by the time of measurement (data not shown). Another possible limitation is selection bias, which could occur if there was confounding or effect modification of the withinmothers prediction of early GWG on final GWG. Inasmuch as the primary sampling frame of the LMU cohort included all deliveries during a defined period, selection bias for this group appears unlikely. The differences between the included and excluded pregnancies in the LMU cohort are explained by our oversampling of overweight and obese mothers. Potential confounding or effect modification by maternal BMI category was explicitly addressed by our stratified analyses. The exclusion criteria might account for selection bias or limitations in external validity. Most exclusions resulted from missing data on prepregnancy weight. There is, however, no reason to assume that the prediction of early weight for total GWG differs between mothers by how assiduously their physicians documented prepregnancy weight. Obese mothers in the PEACHES cohort were recruited from a population similar to that served by the LMU cohort. Therefore it is highly unlikely that obese mothers from the PEACHES cohort differ from those in the LMU cohort. External validity might be limited for pregnancies with premature birth and pregnancies & 2014 Nature America, Inc.
Early prediction of excessive GWG J Knabl et al
355 Table 3. Positive predictive values, negative predictive values, positive and negative likelihood ratios of the week-specific Institute of Medicine/ National Research Council GWG cutoff values for excessive and inadequate GWG in overweight women Excessive GWG Positive predictive value (%) (95% CI) Week Week Week Week Week Week Week Week Week
4/1–8/0 8/1–12/0 12/1–16/0 16/1–20/0 20/1–24/0 24/1–28/0 28/1–32/0 32/1–36/0 36/1–40/0
77.8 89.5 92.5 90.0 88.0 90.0 90.0 91.0 92.0
(52.4; (75.2; (79.6; (77.8; (78.4; (82.2; (83.2; (84.9; (86.2;
93.6) 97.1) 98.4) 96.7) 94.4) 95.0) 94.7) 95.3) 96.0)
Positive likelihood ratio 2.36 4.33 6.78 4.74 3.64 4.41 4.61 5.28 6.04
Inadequate GWG
Negative predictive value (%) (95% CI) 44.9 40.1 43.9 44.5 49.0 60.0 73.6 86.2 92.1
(32.9; (32.1; (35.3; (35.7; (38.9; (48.8; (61.9; (75.3; (82.4;
57.4) 49.9) 52.8) 53.6) 59.2) 70.5) 83.3) 93.5) 97.4)
Negative likelihood ratio
Positive predictive value (%) (95% CI)
Positive likelihood ratio
Negative predictive value (%) (95% CI)
Negative likelihood ratio
0.83 0.74 0.70 0.67 0.52 0.33 0.18 0.08 0.05
13.3 (5.1; 26.8) 10.6 (5.0; 19.2) 11.5 (5.4; 20.8) 13.2 (6.2; 23.6) 17.1 (7.2; 32.1) 31.6 (17.5; 48.7) 48.3 (29.4; 67.5) 58.3 (36.6; 77.9) 81.3 (54.4; 96.0)
1.46 1.50 1.91 1.95 3.07 5.70 12.07 18.80 58.81
94.9 (82.7; 99.4) 96.2 (89.3; 99.2) 97.9 (92.5; 99.7) 96.4 (91.0; 99.0) 97.0 (92.5; 99.2) 98.7 (95.2; 99.8) 100.0 (96.7; 100.0) 100.0 (96.9; 100.0) 99.5 (97.1; 100.0)
0.51 0.50 0.32 0.48 0.46 0.17 0.00 0.00 0.07
Abbreviations: CI, confidence interval; GWG, gestational weight gain.
Table 4. Positive predictive values, negative predictive values, positive and negative likelihood ratios of the week-specific Institute of Medicine/ National Research Council GWG cutoff values for excessive and inadequate GWG in obese women Excessive GWG Positive predictive value (%) (95% CI) Week Week Week Week Week Week Week Week Week
4/1–8/0 8/1–12/0 12/1–16/0 16/1–20/0 20/1–24/0 24/1–28/0 28/1–32/0 32/1–36/0 36/1–40/0
66.7 95.2 93.9 91.7 95.7 94.7 97.8 96.2 96.6
(22.3; (76.2; (79.8; (80.0; (87.8; (86.9; (92.3; (90.6; (91.6;
95.7) 99.9) 99.3) 97.7) 99.1) 98.5) 99.7) 99.0) 99.1)
Positive likelihood ratio 0.98 7.62 6.52 4.79 9.25 7.20 17.26 10.54 11.88
Inadequate GWG
Negative predictive value (%) (95% CI) 32.9 31.5 36.1 40.2 50.6 50.6 61.4 70.8 88.5
(22.5; (23.4; (27.5; (30.8; (39.4; (39.3; (49.0; (58.2; (76.6;
44.6) 40.4) 45.4) 50.1) 61.8) 61.9) 72.8) 81.4) 95.6)
Negative likelihood ratio 1.00 0.83 0.74 0.65 0.41 0.40 0.24 0.17 0.05
Positive predictive value (%) (95% CI) 9.2 17.1 22.5 25.0 34.0 41.9 54.1 65.5 87.5
(3.5; 19.0) (10.5; 25.7) (13.9; 33.2) (15.3; 37.0) (20.9; 49.3) (27.0; 57.9) (36.9; 70.5) (45.7; 82.1) (67.6; 97.3)
Positive likelihood ratio
Negative predictive value (%) (95% CI)
Negative likelihood ratio
0.82 1.41 1.89 2.70 3.69 4.81 7.77 13.99 49.30
82.4 (56.6; 96.2) 96.1 (86.5; 99.5) 95.3 (88.4; 98.7) 99.0 (94.3; 100.0) 96.6 (91.4; 99.1) 96.8 (92.1; 99.1) 97.8 (93.8; 99.5) 98.1 (94.4; 95.6) 98.8 (95.6; 99.8)
1.74 0.28 0.32 0.09 0.26 0.22 0.15 0.15 0.09
Abbreviations: CI, confidence interval; GWG, gestational weight gain.
with GDM. Unfortunately, the numbers were too small to allow for stratified analyses, although assessment of effect modification might be interesting.25 The sensitivity and specificity estimates and the derived LR þ and LR are test characteristics related to the properties of prediction of early GWG and, by definition, can be applied to other populations of pregnancies. The reported PPV and NPV, however, pertain to the a priori risks for excessive and inadequate total GWG for each BMI category in our study population. The a priori risks are reflected by the prevalence of excessive (and inadequate) total GWG in the study population and may differ between populations. The a priori risks in our study population, however, were similar to risks found by other investigators (Weisman et al.26 in women from Central Pennsylvania for excessive GWG, Simas et al.27 in women from Central Massachusetts for inadequate GWG). For populations with different a priori risks, the PPV and NVP values can be calculated based on the reported LR þ and LR (formula shown in Supplementary Material). In summary, our results support the value of weight measurement in pregnancy for early identification of excessive GWG. They also refute the presumption of poor predictive value of early GWG.28 These data provide a basis for counseling mothers on their risk for excessive GWG and for potential-targeted interventions to reduce total GWG. Monitoring of GWG in mothers with adequate GWG early in pregnancy is warranted because excessive GWG may still emerge, particularly in overweight and obese women. & 2014 Nature America, Inc.
CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS We thank Agnes Melita (Department of Obstetrics and Gynecology, LMU Munich Germany) and Andrea Chmitorz (Division of Epidemiology, Institute of Social Paediatrics and Adolescent Medicine, LMU Munich, Germany) for data gathering and data processing. Dr Ensenauer was supported by the German Federal Ministry of Education and Research (BMBF) Grant 0315088.
REFERENCES 1 Rasmussen KM, Yaktine AL (eds). Weight Gain During Pregnancy: Reexamining the Guidelines. Committee to Reexamine IOM Pregnancy Weight Guidelines. National Research Council: Washington, DC, USA, 2009. 2 Nehring I, Schmoll S, Beyerlein A, Hauner H, von Kries R. Gestational weight gain and long-term postpartum weight retention: a meta-analysis. Am J Clin Nutr 2011; 94(5): 1225–1231. 3 Nehring I, Lehmann S, von Kries R. Gestational weight gain in accordance to the IOM/NRC criteria and the risk for childhood overweight: a meta-analysis. Pediatr Obes 2012; 8(3): 218–224. 4 Streuling I, Beyerlein A, Rosenfeld E, Hofmann H, Schulz T, von Kries R. Physical activity and gestational weight gain: a meta-analysis of intervention trials. Br J Obstet Gynaecol 2011; 118(3): 278–284. 5 Streuling I, Beyerlein A, von Kries R. Can gestational weight gain be modified by increasing physical activity and diet counseling? A meta-analysis of interventional trials. Am J Clin Nutr 2010; 92(4): 678–687.
Journal of Perinatology (2014), 351 – 356
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356 6 Thangaratinam S, Rogozinska E, Jolly K, Glinkowski S, Roseboom T, Tomlinson JW et al. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ 2012; 344: e2088. 7 Tanentsapf I, Heitmann BL, Adegboye AR. Systematic review of clinical trials on dietary interventions to prevent excessive weight gain during pregnancy among normal weight, overweight and obese women. BMC Pregnancy Childbirth 2011; 11: 81. 8 Thorsdottir I, Torfadottir JE, Birgisdottir BE, Geirsson RT. Weight gain in women of normal weight before pregnancy: complications in pregnancy or delivery and birth outcome. Obstet Gynecol 2002; 99(5 Part 1): 799–806. 9 Chmitorz A, von Kries R, Rasmussen KM, Nehring I, Ensenauer R. Do trimesterspecific cutoffs predict whether women ultimately stay within the Institute of Medicine/National Research Council guidelines for gestational weight gain? Findings of a retrospective cohort study. Am J Clin Nutr 2012; 95(6): 1432–1437. 10 Ensenauer R, Gmach J, Nehring I, von Kries R. Increased hemoglobin A(1c) in obese pregnant women after exclusion of gestational diabetes. Clin Chem 2012; 58(7): 1152–1154. 11 Ensenauer R. PEACHES Studie. In. Kinderklinik und Kinderpoliklinik im Dr. von Hauner’schen Kinderspital cited. Available from https://www.klinikum. uni-muenchen.de/Peaches-Studie/de/index.html. 12 Daemers DO, Wijnen HA, van Limbeek EB, Bude LM, de Vries RG. Patterns of gestational weight gain in healthy, low-risk pregnant women without co-morbidities. Midwifery 2012; 29(5): 535–541. 13 Beyerlein A, Lack N, von Kries R. Within-population average ranges compared with Institute of Medicine recommendations for gestational weight gain. Obstet Gynecol 2010; 116(5): 1111–1118. 14 Diet, nutrition and the prevention of chronic diseases. World Health Organization Technical Report Series 2003; 916: World Health Organization: Geneva. i-viii, 1–149, backcover. 15 Simel DL, Samsa GP, Matchar DB. Likelihood ratios with confidence: sample size estimation for diagnostic test studies. J Clin Epidemiol 1991; 44(8): 763–770. 16 R Development Core Team. R: A Language and Environment for Statistical Computing. R foundation for statistical computing, 2011; 13(4): 497–512.
17 Stevenson M. epiR: An R package for the analysis of epidemiological data, 2012. R package version 0.9-38 2012. 18 von Kries R, Nehring I. Reproductive endocrinology: reducing gestational weight gain--a panacea? Nat Rev Endocrinol 2012; 8(8): 452–454. 19 Nyaruhucha CN, Msuya JM, Ngowi B, Gimbi DM. Maternal weight gain in second and third trimesters and their relationship with birth weights in Morogoro Municipality, Tanzania. Tanzan Health Res Bull 2006; 8(1): 41–44. 20 Phelan S, Phipps MG, Abrams B, Darroch F, Schaffner A, Wing RR. Randomized trial of a behavioral intervention to prevent excessive gestational weight gain: the Fit for Delivery Study. Am J Clin Nutr 2011; 93(4): 772–779. 21 von Kries R, Chmitorz A, Rasmussen KM, Bayer O, Ensenauer R. Late pregnancy reversal from excessive gestational weight gain lowers risk of childhood overweight-a cohort study. Obesity (Silver Spring) 2012; 21(6): 1232–1237. 22 Wright CS, Weiner M, Localio R, Song L, Chen P, Rubin D. Misreport of gestational weight gain (GWG) in birth certificate data. Matern Child Health J 2012; 16(1): 197–202. 23 Lederman SA, Paxton A. Maternal reporting of prepregnancy weight and birth outcome: consistency and completeness compared with the clinical record. Matern Child Health J 1998; 2(2): 123–126. 24 Mandujano A, Huston-Presley L, Waters TP, Catalano PM. Women’s reported weight: is there a discrepancy? J Matern Fetal Neonatal Med 2012; 25(8): 1395–1398. 25 Carreno CA, Clifton RG, Hauth JC, Myatt L, Roberts JM, Spong CY et al. Excessive early gestational weight gain and risk of gestational diabetes mellitus in nulliparous women. Obstet Gynecol 2012; 119(6): 1227–1233. 26 Weisman CS, Hillemeier MM, Downs DS, Chuang CH, Dyer AM. Preconception predictors of weight gain during pregnancy: prospective findings from the Central Pennsylvania Women’s Health Study. Womens Health Issues 2010; 20(2): 126–132. 27 Simas TA, Liao X, Garrison A, Sullivan GM, Howard AE, Hardy JR. Impact of updated Institute of Medicine guidelines on prepregnancy body mass index categorization, gestational weight gain recommendations, and needed counseling. J Women’s Health (Larchmt) 2011; 20(6): 837–844. 28 Dawes MG, Grudzinskas JG. Repeated measurement of maternal weight during pregnancy. Is this a useful practice? Br J Obstet Gynaecol 1991; 98(2): 189–194.
Supplementary Information accompanies the paper on the Journal of Perinatology website (http://www.nature.com/jp)
Journal of Perinatology (2014), 351 – 356
& 2014 Nature America, Inc.
ORIGINAL ARTICLE
Prediction of excessive gestational weight gain from week-specific cutoff values: a cohort study J Knabl1,5, C Riedel2,5, J Gmach1,2,3,4, R Ensenauer3, L Brandlhuber3, KM Rasmussen4, B Schiessl1 and R von Kries1,2 OBJECTIVE: To assess the prognostic validity of the Institute of Medicine/National Research Council (IOM/NRC) week-specific cutoff values for inadequate or excessive total gestational weight gain (GWG) by 4-week intervals. STUDY DESIGN: We merged data from two German cohorts (LMU cohort (all maternal-weight categories) and PEACHES cohort (obese women)) to provide information on GWG for 749 women (365 normal weight, 199 overweight and 185 obese). We calculated the prognostic values for suboptimal and excessive GWG according to the IOM/NRC cutoff values. RESULT: The positive predictive values for excessive total GWG for those who experienced excessive GWG early in pregnancy was 70.1% (95% confidence interval (CI) 60.5; 78.6) as of week 12/1 to 16/0 in normal-weight women, 89.5% (95% CI 75.2; 97.1) and 95.2 (76.2; 99.9) 95.2% (95% CI 76.2; 99.9) as of week 8/1 to 12/0 for overweight and obese women, respectively. In absence of excessive GWG as of week 12/1 to 16/0, normal-weight women had 77.5% (95% CI 77.1; 83.1) probability of not experiencing excessive total GWG (negative predictive value). In overweight and obese women, the negative predictive value was considerably lower up to week 24/1 to 28/0 (60.0% (95% CI 48.8; 70.5) in week 20/1 to 24/0 and 50.6% (95% CI 39.3; 61.9) in week 24/1 to 28/0). Most women with inadequate GWG in the first and second trimester had adequate total final GWG (positive predictive value for total inadequate GWG o50% up to week 16/1 to 20/0 in all groups). CONCLUSION: As women with excessive weight gain can be identified with high confidence if the GWG exceeds the IOM/NRC week-specific cutoff values, interventions may be initiated early in pregnancy. Journal of Perinatology (2014) 34, 351–356; doi:10.1038/jp.2014.22; published online 27 February 2014 Keywords: pregnancy; excessive weight gain; gestational weight gain; prediction; cohort study
INTRODUCTION Measuring gestational weight gain (GWG) is traditionally part of prenatal care. Current GWG guidelines of the Institute of Medicine (IOM)/National Research Council (NRC) emphasize the importance of adequate weight gain during pregnancy and include weekspecific cutoff values for adequate GWG1 because GWG is an important determinant for fetal and maternal outcomes.2–5 Evidence for the association of inadequate and excessive GWG with maternal and fetal pregnancy outcome is based on total GWG, which can only be determined at term.2–5 Recent metaanalyses have shown that interventions, such as increasing physical activity or nutritional counseling, may assist women to increase or reduce total GWG.6–8 Although some prediction of the risk for excessive total GWG is possible based on the a priori population risk for excessive total GWG, which increases by the body mass index (BMI) category, these a priori risks do not allow for individual counseling and targeted interventions. Individual risks identified early in pregnancy and specific counseling is likely to account for a higher motivation to limit weight gain in the respective mothers than a general statement. Therefore, women at risk of gaining outside the recommended ranges should be identified early in pregnancy so possible interventions can occur. The trimester-specific cutoff
values provided by the IOM/NRC guidelines1 allow identification of women with such outlying GWG values. For counseling of pregnant women one must know the predictive value of these outliers to identify pregnancies at risk for excessive or inadequate total GWG. We previously demonstrated that some prediction of total GWG is possible by trimesterspecific cutoff values.9 For counseling mothers, however, there is a need to strive for more precise prediction. This can be achieved by assessment of the predictive value of week-specific cutoff values. Predictions with tighter intervals are required. The objective of our study was to assess the prognostic validity of the week-specific IOM/NRC cutoff values to predict inadequate or excessive total GWG by 4-week intervals. METHODS We aimed for a precision of ±10% in the predictive values of early GWG in normal-weight, overweight and obese mothers. For predictive values of X75%, this requires 120 women for each maternal-weight category. To allow for a safety margin in case of lower estimates, we aimed to include at least 150 women in each BMI category. We used a three-step strategy to accomplish this. First, between 9 December 2010 and 31 October 2011, 2270 consecutive deliveries, in the Department of Obstetrics and Gynecology of the Ludwig-Maximilians-University
1 Department of Obstetrics and Gynecology, Ludwig-Maximilians-Universita¨t Mu¨nchen, Munich, Germany; 2Division of Epidemiology, Institute of Social Paediatrics and Adolescent Medicine, Ludwig-Maximilians-Universita¨t Mu¨nchen, Munich, Germany; 3Research Center, Dr von Hauner Children’s Hospital, Ludwig-Maximilians-Universita¨t Mu¨nchen, Munich, Germany and 4Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA. Correspondence: Professor R von Kries, Departement of Epidemiology, Institute of Social Paediatrics and Adolescent Medicine, Ludwig-Maximilians-Universita¨t Mu¨nchen, Heiglhofstr. 63, Munich 81377, Germany. E-mail: [email protected] 5 These authors contributed equally to this work. Received 25 September 2013; revised 10 December 2013; accepted 13 January 2014; published online 27 February 2014
Early prediction of excessive GWG J Knabl et al
352 Table 1.
Sample description
Characteristics
Maternal age (years) Height (cm) Prepregnancy weight (kg) BMI categoryd Underweight Normal weight Overweight Obese Birth weight of the child (g) Gestational age (weeks)
Deliveries eligible but not available for the study population (LMU cohortc) n ¼ 977 Mean (s.d.)/ % (n)
Deliveries available for the study population (LMU cohortc) n ¼ 1423 Mean (s.d.)/ % (n)
Deliveries available for the study population (PEACHES cohort) n ¼ 147 Mean (s.d.)/ % (n)
33.1 (5.1) 168.1 (6.6) 63.2 (10.0)
32.2 (5.5)a 167.2 (6.7)a 65.4 (12.6)a
30.6 (5.0)b 168.2 (6.8)b 103.3 (16.6)b
(51) (732) (103) (38)
5.8 (79)a 65.2 (891)a 21.6 (295)a 7.5 (102)a
— — 4.1% (6)b 95.9% (141)b
3193 (714) 38.4 (2.9)
3302 (597)a 39.0 (2.2)a
3488 (474)b 40.1 (1.5)b
5.5 79.2 11.1 4.1
Abbreviations: BMI, body mass index; LMU, Ludwig-Maximilians-University; PEACHES, Programming of Enhanced Adiposity Risk in CHildhood—Early Screening cohort. a Significantly (Po0.05) different from deliveries eligible but were not included in the study population. b Significantly (Po0.05) different from deliveries available for the study population (LMU cohort). c Women who delivered in the Department of Obstetrics and Gynecology of LMU Munich between December 2010 and October 2011, and overweight/obese women who delivered between November 2011 and September 2012. d Differences in number of cases to overall number of cases (977 and 1423) are because of missing values of height and pregregnancy weight in women from the LMU cohort.
Munich (University of Munich, LMU), were considered. During the hospital stay, a research assistant abstracted these mothers’ records on weight gain on most days (except for weekends and holidays). This step allowed recruiting sufficient normal-weight mothers. Second, inasmuch as the proportion of overweight and obese mothers recruited was small, we oversampled overweight and obese mothers in the LMU cohort. The research assistant contacted overweight (BMIX25 and o30 kg m 2) and obese mothers (BMIX30 kg m 2) who had delivered on days when she had not been in hospital by telephone and as well as overweight and obese mothers who delivered between November 2011 and September 2012. She asked both groups of LMU mothers to read the weight-gain values from their pregnancy records. As a result, the LMU cohort included information on GWG for 2400 deliveries. Third, inasmuch as the number of obese mothers was still below our target sample size, we also included obese women who delivered in other hospitals in the catchment area as for the LMU cohort (n ¼ 147 (6 overweight and 141 obese)) from an ongoing observational study on pregnancy outcomes in obese women PEACHES (Programming of Enhanced Adiposity Risk in CHildhood—Early Screening cohort)10,11 in our analysis. This observational prospective study required active involvement of the obese mothers, so only those who volunteered to follow-up visits were included (Table 1). To achieve a homogenous population for analysis, we excluded women who had multiple births, preterm delivery, diagnosis of diabetes mellitus or gestational diabetes mellitus or with missing information on prepregnancy weight, the date of last weight measurement during pregnancy before the 37th week of pregnancy (36/0 week) (Figure 1). We also excluded underweight women because the prevalence of underweight in these birth cohorts was too low for our planned analyses.12,13 Weight-gain values below the 0.1% percentile or above the 99.9% percentile in each gestational month and weight measurements after the 42nd week of pregnancy were defined as implausible and were excluded from analyses (Figure 1). Data on weight gain during pregnancy were read from the ‘maternity notes’, either by the research assistant or by the mother during a telephone interview with the research assistant. In Germany, ‘maternity notes’ are issued to every pregnant woman at her first antenatal visit to the obstetrician. The ‘maternity notes’ include complete documentation of health-care visits during pregnancy. They are an identical copy of all important pregnancyrelated medical records that the patient carries with her for hospital stays or emergencies. Written informed consent was obtained in PEACHES but was not required in the LMU cohort, as this is an anonymous analysis of routine data. The retrospective evaluation of regular medical records was approved by the ethics committee of the LMU Munich, Germany. Total GWG was defined as the difference between a woman’s selfreported prepregnancy weight and the last weight measured before delivery. According to the IOM/NRC guidelines, adequate total GWG was classified as total gain of 12.5 to 18 kg for underweight women, 11.5 to 16 kg for normal-weight women, 7 to 11.5 kg for overweight women and Journal of Perinatology (2014), 351 – 356
5 to 9 kg for obese women.1 Inadequate GWG was defined as GWG values below the recommended GWG and excessive GWG as values above the recommended GWG. The required information on maternal prepregnancy weight and of weight measurement during pregnancy was gathered from the ‘maternity notes’. One gestational interval was defined as 4 weeks, for example, interval 2 was defined as pregnancy week 4/1 days to week 8/0 days. We divided pregnancy into ten 4-week intervals. For example, interval 10 includes the time period from 36 completed gestational weeks and 1 day (36/1 weeks) to 40 completed gestational weeks and 0 days (40/0 weeks). Cutoff points for inadequate and excessive GWG were calculated for each week according to the IOM/NRC guidelines. In these guidelines, GWG increases linearly with different slopes in the first trimester (weeks 1 to 13) and the following two trimesters (weeks 14 to 40).1 Compared with the second and third trimesters, the increments of GWG in the first trimester are smaller. For normal-weight women, for example, the upper cutoff point of adequate GWG in the first trimester is 3 kg. After subtracting from the upper cutoff point of total GWG (16 kg) at the end of pregnancy, the upper limit in the remaining 27 weeks is a total of 13 kg. This results in a weekly gain of 0.23 kg in the first trimester and 0.48 kg in the second and third trimesters. Similarly, the lower cutoff point in the first trimester for normalweight women is 1 kg. Subtracted from the lower cutoff point of total GWG (11.5 kg), the lower limit in the remaining 27 weeks is a total of 10.5 kg. This results in a weekly gain of 0.08 kg in the first trimester and 0.39 kg in the second and third trimesters. To obtain the numeric IOM/NRC upper and lower limits of weight gain for every week, we accumulated the weekly gains according to the underlying formula. For example, in week 18/0 the upper limit was 5.4 kg (3 kg in the first trimester plus 5 weeks 0.48 kg per week) and the lower limit was 2.95 kg (1 kg in the first trimester plus 5 weeks 0.39 kg per week) for normal-weight women. For each woman, we compared her actual cumulative GWG up to the particular week for which data were available in the respective 4-week interval and assessed whether her gain was adequate or below or above the week-specific cutoff points (yes or no). Inasmuch as there are different recommendations for each maternal prepregnancy BMI category, this procedure was conducted separately for each one. BMI was calculated by dividing weight in kilograms by squared height in meters. Categories of BMI were defined according to the IOM/ NRC guidelines and the World Health Organization (WHO) criterion.14 We used t-tests for numeric and Fisher’s exact test for categorical data for comparisons of the characteristics of the subjects. We calculated prognostic values for inadequate and excessive GWG for each gestational interval starting with interval week 4/1 to 8/0 because there were very few observations before 4/1 weeks. The respective interval-specific positive predictive values (PPV) and negative predictive values (NPV) and the positive likelihood ratio (LR þ ) and negative likelihood ratio (LR ) were determined. The PPV’s indicate the proportion & 2014 Nature America, Inc.
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353
Figure 1.
Flow charts of sample size.
of the individuals exposed to excessive or inadequate GWG early in pregnancy who will experience excessive or inadequate GWG, respectively, at delivery. The NPV’s indicate the proportion of the individuals with absence of excessive or inadequate GWG early in pregnancy who will not experience excessive or inadequate GWG, respectively, at delivery. The likelihood ratios (LR) provide a basis to calculate the post-test probabilities for excessive or inadequate total GWG for exceeding week-specific IOM cutoff values (LR þ : for test positives; LR : for test negatives). Exact binomial 95% CI were calculated for PPV and NPV.15 All statistical analyses were conducted using the public domain statistical software R 2.14.2 (ref. 16) (http://cran.r-project.org), with the package epiR.17
RESULTS In the LMU cohort 2400 women were eligible; 1423 of these and the 147 women in the PEACHES cohort provided information on GWG. The application of the exclusion criteria reduced the number of women available for the final analysis to 749 (Figure 1). In the final study population the proportion of pregnancies with excessive total GWG increased with increasing BMI category (38.8%, 64.7% and 65.1% for normal-weight, overweight and obese mothers, respectively). The proportion of pregnancies with inadequate GWG was 18.9% in normal-weight, 6.9% in overweight and 12.9% in obese mothers. There were significant differences between the women from the LMU cohort who were eligible but not available for the study & 2014 Nature America, Inc.
and those from the LMU cohort who were available and provided information (Table 1), reflecting oversampling of overweight and obese women accounting for slightly younger and shorter and heavier mothers and slightly heavier children in the final study population. Prognostic value of the upper cutoff values to predict excessive GWG The PPV indicates the probability for excessive total GWG conditional on exceeding the week-specific IOM/NRC cutoff value by defined 4-week time intervals. For normal-weight mothers, the PPV for excessive total GWG increased continuously from the gestational week 16/0 to week 40/0. PPVs above 70.1% (95% CI 60.5; 78.6) were reached as of week 12/1 to 16/0 (Table 2). This is also reflected in increasing LR þ values. In overweight and obese mothers, the PPV was higher almost throughout pregnancy reaching values above about 89.5% (95% CI 75.2; 97.1) and 95.2% (95% CI 76.2; 99.9) as of week 8/1 to 12/0 (Tables 3 and 4). The prediction for absence of excessive GWG (NPV) at the end of pregnancy from GWG within the IOM/NRC ranges was at or above 77.5% (95% CI 77.1; 83.1) as of the interval week 12/1 to 16/0 in normal-weight women (Table 2), but only exceeded 50% in week 24/1 to 28/0 (60.0% (95% CI 48.8; 70.5) and 20/1 to 24/0 (50.6 % (95% CI 39.4; 61.8) in overweight and obese women, respectively (Tables 3 and 4). Journal of Perinatology (2014), 351 – 356
Early prediction of excessive GWG J Knabl et al
354 Table 2. Positive predictive values, negative predictive values, positive and negative likelihood ratios of the week-specific Institute of Medicine/ National Research Council GWG cutoff values for excessive and inadequate GWG in normal-weight women Excessive GWG Positive predictive value (%) (95% CI) Week Week Week Week Week Week Week Week Week
4/1–8/0 8/1–12/0 12/1–16/0 16/1–20/0 20/1–24/0 24/1–28/0 28/1–32/0 32/1–36/0 36/1–40/0
62.1 61.6 70.1 69.4 73.0 77.2 80.4 81.0 87.6
(48.4; (51.3; (60.5; (59.9; (64.2; (69.2; (73.0; (74.0; (81.3;
74.5) 71.2) 78.6) 77.8) 80.6) 84.0) 86.6) 86.8) 92.4)
Inadequate GWG
Positive likelihood ratio
Negative predictive value (%) (95% CI)
Negative likelihood ratio
Positive predictive value (%) (95% CI)
Positive likelihood ratio
Negative predictive value (%) (95% CI)
Negative likelihood ratio
2.67 2.58 3.65 3.58 4.22 5.30 6.44 6.70 11.20
73.6 (64.8; 81.2) 72.5 (66.0; 78.4) 77.5 (77.1; 83.1) 77.9 (71.9; 83.4) 82.1 (76.1; 87.2) 88.8 (83.3; 92.9) 90.5 (85.6; 94.2) 94.1 (89.9; 96.9) 96.7 (93.3; 98.7)
0.59 0.61 0.45 0.45 0.34 0.20 0.16 0.10 0.05
32.1 (21.9; 43.6) 38.0 (28.8; 47.8) 52.8 (40.7; 64.7) 46.9 (35.7; 58.3) 63.2 (50.7; 74.6) 74.1 (60.3; 85.0) 80.0 (67.7; 89.2) 83.6 (71.2; 92.2) 95.0 (86.1; 99.0)
2.01 2.50 4.70 3.92 7.10 11.79 17.17 21.95 81.51
91.1 (83.8; 95.8) 90.1 (85.1; 93.8) 91.1 (86.7; 94.4) 91.5 (87.1; 94.7) 92.4 (88.4; 95.4) 91.4 (87.4; 94.5) 94.0 (90.6; 96.5) 92.8 (89.3; 95.3) 96.1 (93.2; 98.0)
0.42 0.45 0.41 0.41 0.34 0.39 0.27 0.33 0.18
Abbreviations: CI, confidence interval; GWG, gestational weight gain.
Prognostic value of the lower cutoff values to predict inadequate GWG Inadequate GWG in the first and second trimester of pregnancy was a poor predictor for total inadequate GWG irrespective of maternal prepregnancy BMI category. Conversely, inadequate total GWG was unlikely if GWG was within the recommended ranges early in pregnancy (Tables 2–4).
DISCUSSION We found that women with normal GWG in early pregnancy were unlikely to experience inadequate GWG, but could still gain above the GWG guidelines. Women with excessive GWG early in pregnancy were highly likely to develop excessive total GWG and may benefit from an intervention to help them to gain within the guidelines. In contrast, women with inadequate GWG early in pregnancy had a fair chance to gain within the GWG guidelines without specific intervention. Our data allow for precise and early identification of women at risk for excessive GWG, a prerequisite for counseling and implementation of targeted interventions. To our knowledge, there is only one study on the prognostic value for exceeding IOM/NRC recommendations early in pregnancy. This study was based on prediction by trimester only.9 The reported trimester-specific predictive values might be overestimates because of methodological limitations of the study.9 Here, we had adequate numbers of women in all studied maternal prepregnancy BMI categories to develop PPVs with high precision, which allows physicians to counsel their patients with confidence. Women who are at risk for excessive or inadequate GWG must be identified so as to assign them to the appropriate intervention. The importance of risk-guided counseling for excessive and inadequate GWG has recently been outlined.18 Targeted interventions are mandatory. According to the largest meta-analysis to date,6 reducing GWG is not beneficial for all pregnant women, and would be harmful for those with suboptimal GWG or weight loss.7,18 In our study, prediction of inadequate total GWG from inadequate GWG early in pregnancy was poor, so targeted interventions to increase GWG in such pregnancies may not appear justified in affluent countries as Germany. This may not be the case in poorer countries.19 In contrast, excessive GWG early in pregnancy—especially for overweight and obese women—is a good predictor of excessive total GWG and should prompt interventions. This is especially important because early excessive GWG is rarely reversible without special interventions.20 According to a recent Journal of Perinatology (2014), 351 – 356
meta-analysis,5 interventions to limit excessive GWG are likely to be effective and might also reduce the risk for poor pregnancy outcomes and later overweight of the child. In a recent observational study, reversal from excessive GWG in the first two trimesters to normal in the third trimester was associated with a reversal of the risk for childhood overweight related to excessive GWG.21 Therefore interventions to avoid excessive GWG in mothers at risk of excessive GWG appear warranted. The key elements of such interventions are weight monitoring, increasing physical activity and dietary counseling, as observed in some meta-analyses.4,6 Our study population had the major advantage of a sufficient number of weight measurements for each woman in the relevant maternal BMI categories. The major strength of our findings is their high precision for prediction of excessive GWG from early GWG in all maternal-weight categories. All data for this study were obtained from medical records. All weight data apart from prepregnancy weight, which was recalled at the time of the first antenatal visit, were measured. This is important because self-recall of weight during pregnancy may cause misclassification of GWG,22 whereas recall of prepregnancy weight seems to be more reliable.23 Underestimation of selfreported prepregnancy weight and, therefore, overestimation of GWG (as shown elsewhere24) appears unlikely in our data, however, because of a close correlation of the reported prepregnancy weight and the first weight measured in pregnancy, which approximated the expected mean weight gain by the time of measurement (data not shown). Another possible limitation is selection bias, which could occur if there was confounding or effect modification of the withinmothers prediction of early GWG on final GWG. Inasmuch as the primary sampling frame of the LMU cohort included all deliveries during a defined period, selection bias for this group appears unlikely. The differences between the included and excluded pregnancies in the LMU cohort are explained by our oversampling of overweight and obese mothers. Potential confounding or effect modification by maternal BMI category was explicitly addressed by our stratified analyses. The exclusion criteria might account for selection bias or limitations in external validity. Most exclusions resulted from missing data on prepregnancy weight. There is, however, no reason to assume that the prediction of early weight for total GWG differs between mothers by how assiduously their physicians documented prepregnancy weight. Obese mothers in the PEACHES cohort were recruited from a population similar to that served by the LMU cohort. Therefore it is highly unlikely that obese mothers from the PEACHES cohort differ from those in the LMU cohort. External validity might be limited for pregnancies with premature birth and pregnancies & 2014 Nature America, Inc.
Early prediction of excessive GWG J Knabl et al
355 Table 3. Positive predictive values, negative predictive values, positive and negative likelihood ratios of the week-specific Institute of Medicine/ National Research Council GWG cutoff values for excessive and inadequate GWG in overweight women Excessive GWG Positive predictive value (%) (95% CI) Week Week Week Week Week Week Week Week Week
4/1–8/0 8/1–12/0 12/1–16/0 16/1–20/0 20/1–24/0 24/1–28/0 28/1–32/0 32/1–36/0 36/1–40/0
77.8 89.5 92.5 90.0 88.0 90.0 90.0 91.0 92.0
(52.4; (75.2; (79.6; (77.8; (78.4; (82.2; (83.2; (84.9; (86.2;
93.6) 97.1) 98.4) 96.7) 94.4) 95.0) 94.7) 95.3) 96.0)
Positive likelihood ratio 2.36 4.33 6.78 4.74 3.64 4.41 4.61 5.28 6.04
Inadequate GWG
Negative predictive value (%) (95% CI) 44.9 40.1 43.9 44.5 49.0 60.0 73.6 86.2 92.1
(32.9; (32.1; (35.3; (35.7; (38.9; (48.8; (61.9; (75.3; (82.4;
57.4) 49.9) 52.8) 53.6) 59.2) 70.5) 83.3) 93.5) 97.4)
Negative likelihood ratio
Positive predictive value (%) (95% CI)
Positive likelihood ratio
Negative predictive value (%) (95% CI)
Negative likelihood ratio
0.83 0.74 0.70 0.67 0.52 0.33 0.18 0.08 0.05
13.3 (5.1; 26.8) 10.6 (5.0; 19.2) 11.5 (5.4; 20.8) 13.2 (6.2; 23.6) 17.1 (7.2; 32.1) 31.6 (17.5; 48.7) 48.3 (29.4; 67.5) 58.3 (36.6; 77.9) 81.3 (54.4; 96.0)
1.46 1.50 1.91 1.95 3.07 5.70 12.07 18.80 58.81
94.9 (82.7; 99.4) 96.2 (89.3; 99.2) 97.9 (92.5; 99.7) 96.4 (91.0; 99.0) 97.0 (92.5; 99.2) 98.7 (95.2; 99.8) 100.0 (96.7; 100.0) 100.0 (96.9; 100.0) 99.5 (97.1; 100.0)
0.51 0.50 0.32 0.48 0.46 0.17 0.00 0.00 0.07
Abbreviations: CI, confidence interval; GWG, gestational weight gain.
Table 4. Positive predictive values, negative predictive values, positive and negative likelihood ratios of the week-specific Institute of Medicine/ National Research Council GWG cutoff values for excessive and inadequate GWG in obese women Excessive GWG Positive predictive value (%) (95% CI) Week Week Week Week Week Week Week Week Week
4/1–8/0 8/1–12/0 12/1–16/0 16/1–20/0 20/1–24/0 24/1–28/0 28/1–32/0 32/1–36/0 36/1–40/0
66.7 95.2 93.9 91.7 95.7 94.7 97.8 96.2 96.6
(22.3; (76.2; (79.8; (80.0; (87.8; (86.9; (92.3; (90.6; (91.6;
95.7) 99.9) 99.3) 97.7) 99.1) 98.5) 99.7) 99.0) 99.1)
Positive likelihood ratio 0.98 7.62 6.52 4.79 9.25 7.20 17.26 10.54 11.88
Inadequate GWG
Negative predictive value (%) (95% CI) 32.9 31.5 36.1 40.2 50.6 50.6 61.4 70.8 88.5
(22.5; (23.4; (27.5; (30.8; (39.4; (39.3; (49.0; (58.2; (76.6;
44.6) 40.4) 45.4) 50.1) 61.8) 61.9) 72.8) 81.4) 95.6)
Negative likelihood ratio 1.00 0.83 0.74 0.65 0.41 0.40 0.24 0.17 0.05
Positive predictive value (%) (95% CI) 9.2 17.1 22.5 25.0 34.0 41.9 54.1 65.5 87.5
(3.5; 19.0) (10.5; 25.7) (13.9; 33.2) (15.3; 37.0) (20.9; 49.3) (27.0; 57.9) (36.9; 70.5) (45.7; 82.1) (67.6; 97.3)
Positive likelihood ratio
Negative predictive value (%) (95% CI)
Negative likelihood ratio
0.82 1.41 1.89 2.70 3.69 4.81 7.77 13.99 49.30
82.4 (56.6; 96.2) 96.1 (86.5; 99.5) 95.3 (88.4; 98.7) 99.0 (94.3; 100.0) 96.6 (91.4; 99.1) 96.8 (92.1; 99.1) 97.8 (93.8; 99.5) 98.1 (94.4; 95.6) 98.8 (95.6; 99.8)
1.74 0.28 0.32 0.09 0.26 0.22 0.15 0.15 0.09
Abbreviations: CI, confidence interval; GWG, gestational weight gain.
with GDM. Unfortunately, the numbers were too small to allow for stratified analyses, although assessment of effect modification might be interesting.25 The sensitivity and specificity estimates and the derived LR þ and LR are test characteristics related to the properties of prediction of early GWG and, by definition, can be applied to other populations of pregnancies. The reported PPV and NPV, however, pertain to the a priori risks for excessive and inadequate total GWG for each BMI category in our study population. The a priori risks are reflected by the prevalence of excessive (and inadequate) total GWG in the study population and may differ between populations. The a priori risks in our study population, however, were similar to risks found by other investigators (Weisman et al.26 in women from Central Pennsylvania for excessive GWG, Simas et al.27 in women from Central Massachusetts for inadequate GWG). For populations with different a priori risks, the PPV and NVP values can be calculated based on the reported LR þ and LR (formula shown in Supplementary Material). In summary, our results support the value of weight measurement in pregnancy for early identification of excessive GWG. They also refute the presumption of poor predictive value of early GWG.28 These data provide a basis for counseling mothers on their risk for excessive GWG and for potential-targeted interventions to reduce total GWG. Monitoring of GWG in mothers with adequate GWG early in pregnancy is warranted because excessive GWG may still emerge, particularly in overweight and obese women. & 2014 Nature America, Inc.
CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS We thank Agnes Melita (Department of Obstetrics and Gynecology, LMU Munich Germany) and Andrea Chmitorz (Division of Epidemiology, Institute of Social Paediatrics and Adolescent Medicine, LMU Munich, Germany) for data gathering and data processing. Dr Ensenauer was supported by the German Federal Ministry of Education and Research (BMBF) Grant 0315088.
REFERENCES 1 Rasmussen KM, Yaktine AL (eds). Weight Gain During Pregnancy: Reexamining the Guidelines. Committee to Reexamine IOM Pregnancy Weight Guidelines. National Research Council: Washington, DC, USA, 2009. 2 Nehring I, Schmoll S, Beyerlein A, Hauner H, von Kries R. Gestational weight gain and long-term postpartum weight retention: a meta-analysis. Am J Clin Nutr 2011; 94(5): 1225–1231. 3 Nehring I, Lehmann S, von Kries R. Gestational weight gain in accordance to the IOM/NRC criteria and the risk for childhood overweight: a meta-analysis. Pediatr Obes 2012; 8(3): 218–224. 4 Streuling I, Beyerlein A, Rosenfeld E, Hofmann H, Schulz T, von Kries R. Physical activity and gestational weight gain: a meta-analysis of intervention trials. Br J Obstet Gynaecol 2011; 118(3): 278–284. 5 Streuling I, Beyerlein A, von Kries R. Can gestational weight gain be modified by increasing physical activity and diet counseling? A meta-analysis of interventional trials. Am J Clin Nutr 2010; 92(4): 678–687.
Journal of Perinatology (2014), 351 – 356
Early prediction of excessive GWG J Knabl et al
356 6 Thangaratinam S, Rogozinska E, Jolly K, Glinkowski S, Roseboom T, Tomlinson JW et al. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ 2012; 344: e2088. 7 Tanentsapf I, Heitmann BL, Adegboye AR. Systematic review of clinical trials on dietary interventions to prevent excessive weight gain during pregnancy among normal weight, overweight and obese women. BMC Pregnancy Childbirth 2011; 11: 81. 8 Thorsdottir I, Torfadottir JE, Birgisdottir BE, Geirsson RT. Weight gain in women of normal weight before pregnancy: complications in pregnancy or delivery and birth outcome. Obstet Gynecol 2002; 99(5 Part 1): 799–806. 9 Chmitorz A, von Kries R, Rasmussen KM, Nehring I, Ensenauer R. Do trimesterspecific cutoffs predict whether women ultimately stay within the Institute of Medicine/National Research Council guidelines for gestational weight gain? Findings of a retrospective cohort study. Am J Clin Nutr 2012; 95(6): 1432–1437. 10 Ensenauer R, Gmach J, Nehring I, von Kries R. Increased hemoglobin A(1c) in obese pregnant women after exclusion of gestational diabetes. Clin Chem 2012; 58(7): 1152–1154. 11 Ensenauer R. PEACHES Studie. In. Kinderklinik und Kinderpoliklinik im Dr. von Hauner’schen Kinderspital cited. Available from https://www.klinikum. uni-muenchen.de/Peaches-Studie/de/index.html. 12 Daemers DO, Wijnen HA, van Limbeek EB, Bude LM, de Vries RG. Patterns of gestational weight gain in healthy, low-risk pregnant women without co-morbidities. Midwifery 2012; 29(5): 535–541. 13 Beyerlein A, Lack N, von Kries R. Within-population average ranges compared with Institute of Medicine recommendations for gestational weight gain. Obstet Gynecol 2010; 116(5): 1111–1118. 14 Diet, nutrition and the prevention of chronic diseases. World Health Organization Technical Report Series 2003; 916: World Health Organization: Geneva. i-viii, 1–149, backcover. 15 Simel DL, Samsa GP, Matchar DB. Likelihood ratios with confidence: sample size estimation for diagnostic test studies. J Clin Epidemiol 1991; 44(8): 763–770. 16 R Development Core Team. R: A Language and Environment for Statistical Computing. R foundation for statistical computing, 2011; 13(4): 497–512.
17 Stevenson M. epiR: An R package for the analysis of epidemiological data, 2012. R package version 0.9-38 2012. 18 von Kries R, Nehring I. Reproductive endocrinology: reducing gestational weight gain--a panacea? Nat Rev Endocrinol 2012; 8(8): 452–454. 19 Nyaruhucha CN, Msuya JM, Ngowi B, Gimbi DM. Maternal weight gain in second and third trimesters and their relationship with birth weights in Morogoro Municipality, Tanzania. Tanzan Health Res Bull 2006; 8(1): 41–44. 20 Phelan S, Phipps MG, Abrams B, Darroch F, Schaffner A, Wing RR. Randomized trial of a behavioral intervention to prevent excessive gestational weight gain: the Fit for Delivery Study. Am J Clin Nutr 2011; 93(4): 772–779. 21 von Kries R, Chmitorz A, Rasmussen KM, Bayer O, Ensenauer R. Late pregnancy reversal from excessive gestational weight gain lowers risk of childhood overweight-a cohort study. Obesity (Silver Spring) 2012; 21(6): 1232–1237. 22 Wright CS, Weiner M, Localio R, Song L, Chen P, Rubin D. Misreport of gestational weight gain (GWG) in birth certificate data. Matern Child Health J 2012; 16(1): 197–202. 23 Lederman SA, Paxton A. Maternal reporting of prepregnancy weight and birth outcome: consistency and completeness compared with the clinical record. Matern Child Health J 1998; 2(2): 123–126. 24 Mandujano A, Huston-Presley L, Waters TP, Catalano PM. Women’s reported weight: is there a discrepancy? J Matern Fetal Neonatal Med 2012; 25(8): 1395–1398. 25 Carreno CA, Clifton RG, Hauth JC, Myatt L, Roberts JM, Spong CY et al. Excessive early gestational weight gain and risk of gestational diabetes mellitus in nulliparous women. Obstet Gynecol 2012; 119(6): 1227–1233. 26 Weisman CS, Hillemeier MM, Downs DS, Chuang CH, Dyer AM. Preconception predictors of weight gain during pregnancy: prospective findings from the Central Pennsylvania Women’s Health Study. Womens Health Issues 2010; 20(2): 126–132. 27 Simas TA, Liao X, Garrison A, Sullivan GM, Howard AE, Hardy JR. Impact of updated Institute of Medicine guidelines on prepregnancy body mass index categorization, gestational weight gain recommendations, and needed counseling. J Women’s Health (Larchmt) 2011; 20(6): 837–844. 28 Dawes MG, Grudzinskas JG. Repeated measurement of maternal weight during pregnancy. Is this a useful practice? Br J Obstet Gynaecol 1991; 98(2): 189–194.
Supplementary Information accompanies the paper on the Journal of Perinatology website (http://www.nature.com/jp)
Journal of Perinatology (2014), 351 – 356
& 2014 Nature America, Inc.
