Table 3.

Studies about the effects of eating disorders on pregnancy and fetal outcomes.

Author (year)	References	Aim of study	Type of study. population	Maternal and fetal outcomes	Key results
Blais et al. (2000)	(83)	To assess the impact of eating disorders (EDs: AN or BN) on pregnancy outcomes and the impact of pregnancy on cognitive and behavioral symptoms of EDs	Prospective study N = 54 United States	EDs women showed spontaneous abortion, therapeutic abortion and live birth	High rate of therapeutic abortion in EDs population
Franko et al. (2001)	(84)	To report obstetrical outcomes in a group of women with AN or BN	Prospective study Pregnant women with ED (AN and BN) n = 49 United States	Pregnant women with active EDs appear to be at greater risk for delivery by cesarean section and for postpartum depression	Pregnant women with EDs appear to be at greater risk for delivery by cesarean section (41 vs. 12%) and for postpartum depression (45 vs. 29%). Higher rate of birth defects (n = 3, 6.1%) No differences in rates of prematurity, Apgar score, or infant birth weight
Park et al. (2003)	(30)	To review evidence in genetic factors, pregnancy, the perinatal and postpartum period, infancy, and the early years, focusing on feeding and mealtimes, general parenting functions and growth	Review	ED pregnant women had higher rate of miscarriages, intra-uterine growth restriction, low infant birth weight, prematurity, perinatal mortality, lower Apgar score, and congenital abnormalities	- AN with low pre-pregnancy weight and low GWG have been associated with low infant birth weight, prematurity, perinatal mortality, lower Apgar score, congenital abnormalities - BN had a higher rate of miscarriages, intra-uterine growth restriction and congenital malformation - 5 possible mechanisms: genetic influences and gene-environment interactions, parental eating psychopathology may impinge directly on the child, disrupt general parenting functioning, learnt behavior, discordant marital, and family relationship
Sollid et al. (2004)	(85)	To determine the association of an ED diagnosed before pregnancy and a preterm delivery and/or the delivery of a low-birth-weight or small-for-gestational-age infant	Hospitalization records (more severe cases) Case-control prospective study (504 vs. 1,552) Danish population	ED pregnant women had a higher rate of low-birth-weight infant, preterm delivery, and SGA infants	- ED had Greater risk of Lower BW(OR, 2.2; 95% CI, 1.4–3.2), preterm delivery (OR, 1.7; 95% CI, 1.1–2.6), SGA (OR, 1.8; 95% CI, 1.3–2.4) - The risk of a low BW infant was twice as high in women with a previous ED compared with women with no such disorder - The risk of preterm delivery and a SGA infant was increased to 70% - Not mention to BMI, very severe cases
Kouba et al. (2005)	(82)	To examine pregnancy and neonatal outcomes in women with past or current eating disorders	Prospective case-control N = 97 Controls n = 68 Cases n = 49 (24 AN, 20 BN, 5 EDNOS) (Stockholm)	ED was associated to higher incidence of SGA, low birth weight, smaller head circumference and microcephaly	- SGA: 12 vs. 1%, p < 0.005 - Low birth weight (g): AN 3,210 ± 533 vs. controls 3,516 ± 515, p < 0.05 - Head circumference (cm): AN 33.7 ± 1.6, BN 33.7 ± 1.0, vs. controls 35.2 ± 1.6, both p < 0.001 - Microcephaly: ED 8% vs. controls 0%, p < 0.005 - IUGR: ED 8% vs. controls 0%, p = 0.07 - GA (weeks): ED 38.9 ± 1.8 vs. controls 39.2 ± 1.8, p = 0.043
Ekéus et al. (2006)	(86)	To examine birth outcomes and pregnancy complications in women with a history of AN	Prospective cohort study, Nationwide, Sweden Primiparous discharged from hospital with a diagnosisof AN vs. primiparous with no AN AN = 828,582 Controls = 827,582	Past history of AN was not associated with negative birth outcomes	- Mean birthweight (g): AN 3,387 vs. controls 3,431 g, p < 0.005. Non-adjusted by sex and GA - Small for gestational age (adjusted by sex and GA): no differences - Main birth outcome measures in women with a history of AN were very similar to the main population - Discrete lower BW
Newton and Chizawsky (2006)	(87)	To review the adverse fetal, birth, and maternal outcomes because of EDs. To enhance standard assessment practice and facilitate early intervention for the ED patient	Review	EDs had been associated to intrauterine growth retardation, premature birth, congenital anomalies, perinatal mortality, low birth weight, and microcephaly	ED had a higher risk of intrauterine growth retardation, premature birth, congenital anomalies (cleft lip and palate), perinatal mortality, low birth weight and microcephaly
Morgan et al. (2006)	(88)	To assess the impact of active BN in obstetric outcomes vs. quiescent BN	Retrospective Case-control study n = 122 Control = 89 UK	Active BN increase the risk of miscarriage and premature delivery	Active BN: - Higher % of unplanned pregnancies - Higher ORs for postnatal depression, miscarriage, and preterm delivery were 2.8 (95% [CI], 1.2–6.2), 2.6 (95% CI, 1.2–5.6) and 3.3 (95% CI, 1.3–8.8), respectively, GD (OR 5.7, 95% CI 1.2–26.6) and also hyperemesis
Micali et al. (2007)	(89)	To determine whether women with a history of eating disorders are at higher risk of major adverse perinatal outcome	Longitudinal cohort study (ALSPAC) UK AN = 171, BN = 199, AN+BN = 82 n = 10,636 unexposed	EDs had not an increased rate of preterm delivery. BN has been associated to miscarriage and AN to smaller birthweight babies	-BN was associated with miscarriage (relative risk ratio 2). Also, after adjusted for lifetime smoking and alcohol use, age and parity (OR 1,4 ((95% CI 1.1–2.0), p < 0.05) - AN had smaller babies (p < 0.05). It may be mediated by lower pre-pregnancy BMI and to a lesser extent by smoking in the second trimester of pregnancy. - Preterm delivery: AN 6.5%, BN 5.0%, AN+BN 4.9%, other psychiatric disorders 5.8%, general population 4.8%. After controlling for ethnicity, maternal age, and parity, Not differences between ED and general population. - Other psychiatric disorders group had higher rates compared with the general population (OR 1.3, 95% CI 1.0–1.8, p = 0.03). - No differences in preterm delivery
Bridget (2008)	(28)	To review the effect of ED in pregnancy and fetal outcomes	Review	ED had been associated to miscarriage, intrauterine growth retardation, premature birth, low birth weight, and microcephaly	BN: miscarriage AN: smaller babies, SGA, microcephaly, intrauterine growth restriction, and premature delivery (especially if the mother's body mass index was 20)
Bansil et al. (2008)	(90)	To describe trends in the prevalence of EDs among delivery hospitalizations in the United States from 1994 to 2004 and to compare hospital, demographic, and obstetrical outcomes among women with and without EDs	Retrospective n = 1,668 United States	Women with EDs are at increased risk of adverse pregnancy outcomes including fetal growth restriction, preterm labor, anemia, and genitourinary tract infections	Delivery hospitalizations with an ED were significantly more likely than those without an ED to have fetal growth restriction (odds ratio [OR] 9.08, 95% confidence interval [CI] 6.45–12.77), preterm labor (OR 2.78, 95% CI 2.10–3.69), anemia (OR 1.73, 95% CI 1.25–2.38), genitourinary tract infections (OR 1.66, 95% CI 1.03–2.68), and labor induction (OR 1.32, 95% CI 1.01–1.73)
Bulik et al. (2009)	(91)	To assess the association between EDs (AN, BN, BED, EDNOS-P) and pregnancy outcomes, controlled by confounding variables (GA, maternal age, income, education, parity, GWG) To assess the association with secondary outcomes (epidural, induction, placenta previa, non-vertex cephalic presentation)	MoBa study. Prospective cohort (n = 35,929), volunteered participation (42%). ED in the 6-months prior to or during pregnancy (AN n = 35, BN n = 304, BED n = 1,812, EDNOS-P n = 36) vs. referent group (n = 33,742)	ED was not associated to an increased rate of preterm delivery. BED is associated to a lower risk of small for gestational age babies and a higher risk of large for gestational age	- BED adjusted by gestational age, maternal age, income, education, and parity: Lower risk of SGA OR 0.65 (95% CI: 0.52, 0.8) p < 0.01, and after adjusting by smoking OR 0.63 (95% CI 0.51, 0.79) p < 0.01. Large for gestational age OR 1.2 (95% CI: 1.1, 1.4), p = 0.02, and after adjusting by smoking OR 1.2 (95% CI: 1.1, 1.4), p = 0.02 Preterm delivery OR 1.1 (95% IC: 0.92, 1.4) p = 0.65 - BED: higher% of LGA and c-section, lower% of SGA Not significant results on AN (low prevalence n = 35) - Preterm delivery adjusted by gestational age, maternal age, income, education, and parity: - AN: OR 0.63 (95% CI: 0.091, 4.3) p = 0.91 - BN: OR 0.78 (95% CI: 0.42, 1.4) p = 0.88
Bulik et al. (2010)	(42)	To assess unplanned pregnancy in AN patients	MoBA cohort AN = 62 vs. unexposed = 46,893	ED showed more unplanned pregnancies and induced abortion	RR 2.2 (95% CI, 1.64–2.72) of unintended pregnancies among AN Higher induced abortion (24.2 vs. 14.6%)
Pasternak et al. (2011)	(92)	To assess whether EDs (AN, BN or EDNOS) have an increased risk for adverse obstetric and perinatal outcomes	Retrospective Population-based study ED = 122 (AN = 41BN = 62 EDNOS = 19)vs. controls = 117,875 Israel	Eating disorders are associated with increased risk of adverse pregnancy outcomes	EDs patients were at risk of Low BW (OR 2.5, 95% CI 1.3–5.0), Preterm delivery (OR 2.2, 95% CI 1.4–3.6) and C-section (OR 1.9, 95% CI 1.3–2.9) Include severe cases
Eagles et al. (2012)	(93)	To compare pregnancy outcomes of women with and without a history of AN	Prospective case-control matched (1 case: 5 controls) by age, parity and year of birth (1965–2007) n = 804 Controls n = 670 women-−1,144 babies Cases (AN) n = 134 women-−230 babies Scotland	AN had a higher incidence of IUGR	AN were at risk of IUGR: RR 1.54, 95% CI 1.11–2.13
Linna et al. (2013)	(51)	To assess how eating disorders are related to reproductive health outcomes in a representative patient population	Retrospective EDs n = 2,257 Controls n = 9,028 Helsinki	EDs were associated with increased risk of induced abortion and miscarriage compared to controls	-Women with BED were more than 3 times as likely to have a miscarriage than controls [odds ratio (OR) 3.18; 95% confidence interval (CI) 1.52–6.66]. - Women with atypical BN, defined as those with one or more absent features of typical BN, were 44% more likely to have a miscarriage than controls (OR 1.44; 95% CI 1.02–2.04)
Solmi et al. (2014)	(94)	To quantify the effect of maternal AN (active or past) on birth weight	Systematic review (14 studies) Meta-analysis (9 studies) 1999–2012	AN was associated to smaller birthweight but with an important methodological heterogeneity between studies	Systematic Review: AN and other Eds were associated with smaller birthweight, differences found from −198 to −306 g. Nevertheless, the most of the studies don't adjust by sex and gestational age; after this adjustment, differences were smaller. - Meta-analysis (active or past AN): a standardized mean difference of weight: −0.19 kg (95% CI: −0.25, −0.15; P = 0.01) - Good evidence of heterogeneity in the studies (χ2 = 18.79, P = 0.016; I2 = 57.4%)
Linna et al. (2014)	(95)	To assess pregnancy, obstetric, and perinatal health outcomes and complications in women with lifetime ED	Prospective case-control population—based study N = 7,379 Controls n = 6,319 Cases n = 1,078 (AN = 302, BN = 724, BED = 52) Helsinki	AN and BN were associated with lower birthweight. AN was also associated with IUGR, preterm delivery and perinatal death. BN was also associated to lower Apgar score at 1 min and need of resuscitation. BED was associated to higher birthweight and to large for gestational age.	- AN and BN had significantly lower BW babies (mean 3,302 g [SD 562], adjusted p < 0.001 in AN, mean 3,464 g [563], adjusted p = 0.037 in BN, mean 3,520 g [539] in unexposed women) -BED had higher weight babies (mean 3,812 g [519], adjusted p < 0.001). - AN was significantly associated with anemia, slow fetal growth (OR 2.59, 95% CI 1.43–4.71), small for gestational age (OR 2.20, 95% CI 1.23–3.93) premature contractions, very premature birth (OR 4.59, 95% CI 1.25–16.87), and perinatal death (adjusted OR 4.06, 95% CI 1.15–14.35). -BN was associated with premature contractions (OR 2.2, 95% CI 1.17–4.14), resuscitations of the neonate (OR 2.12, 95% CI 1.18–3.79), and a lowAPGAR score (OR 2.31, 95% CI 1.34–3.98) - BED was associated with maternal hypertension (OR 4.32, 95% CI 1.64–11.36)
Koubaa et al. (2015)	(67)	To investigate serum biomarkers of nutrition and stress in pregnant women with a previous ED compared to controls and in relation to head circumference and early neurocognitive development of the offspring	Prospective case-control N = 96 Controls n = 59 Cases n = 37 (AN 20, BN 17) Sweden	EDs were associated to smaller head circumference even having the same serum levels of free thyroxine. AN group had a positive correlation between cortisol and head circumference	- Maternal serum levels of free thyroxine were similar between groups but correlated positively to reduced head circumference at birth of the children in the BN group (r = 0.48, p < 0.05), and with the same tendency in the AN group (r = 0.42, p = 0.07), but not in the controls (r = 0.006) - However, in the combined patient group, maternal free T4 correlated positively to head circumference at birth (rp = 0.36, p < 0.05), as in the BN group (rp = 0.48, p < 0.05), and with a similar tendency in the AN group (rp = 0.42, p = 0.07), - Cortisol levels were comparable between groups with the highest mean value in the control group. In the AN group only, there was a positive correlation between cortisol and head circumference of the offspring at birth (rs = 0.49, p < 0.05) - Head circumference (cm): AN 33.6 ± 1.6, BN 33.8 ± 0.88, control 35.2 ± 1.6, both p < 0.005 - Serum levels of IGF-I SD-score correlated positively with head circumference of the offspring at birth in the patient group (rs = 0.38, p < 0.05) but not in the separate groups
Triunfo and Lanzon (2015)	(96)	To review the associations between maternal undernutrition and obstetric risks	Literature review	Maternal undernutrition is associated to fetal growth restriction	Low intake of dietary nutrients determines a fetal growth restriction, may be due to an alteration in fetal hormones
Micali et al. (2016)	(97)	To investigate whether EDs are associated with lower size at birth, symmetric growth restriction, and preterm birth; and whether pregnancy smoking explains the association between AN and fetal growth	Prospective case-control N = 80,660 Controls n = 76,724 Cases n = 3,936 (AN 1,609, BN 1,693, AN+BN 634) UK	EDs, specially AN, had a negative impact in fetal growth and prematurity. Pregnancy smoking only partly explained the association between AN and adverse fetal outcomes	-IUGR: AN and AN+ BN: OR 1.6 [95% CI 1.3–1.8] - SGA: AN and AN+BN: OR 1.5 [95% CI 1.2–1.9). AN (15.5%) vs. controls (10.4%): OR 2.90 (95% CI 1.98–4.26). Lower birthweight was more associated with active AN than past AN, and it was lower than controls - Prematurity: Active AN + past AN: not differences on prematurity rates. Active AN: double rates of prematurity than past AN (7.51 vs. 4.11%). Active AN increased rates prematurity vs. controls (OR 1.77, 95% CI 1.00–3.12; p = 0.049). BN: not differences vs. controls
Kimmel et al. (2016)	(27)	To summarizes the literature on obstetric and gynecologic complications associated with EDs	Literature review	No consistent informations about fetal consequences of pregnancy women with eating disorders were found	Small samples studies report association between AN and increased risk of miscarriage, preterm birth, low birth weight infants, SGA infants, small head circumference, microcephaly, lower Apgar scores at 5 min, and greater risk of perinatal mortality. BN was associated with preterm birth and lower Apgar scores at 1-min. Bigger samples studies report contradictories results. Some studies affirm that women with ED (AN or BN) have increased rates of fetal growth restriction, preterm delivery, very premature birth, SGA, low birth weight, and perinatal death. While others cohort studies from different places of the world have consistently demonstrated no significant difference in adverse perinatal outcomes
Easter et al. (2017)	(98)	To investigate HPA axis regulation in women with Eds or their infants during the perinatal period	Prospective longitudinal study EDs = 47 Controls = 44 UK	During pregnancy women with ED had lower cortisol declines, suggestive of blunted diurnal cortisol rhythms. Postnatally, their infants also had a heightened response to stress	- Women with current ED (C-ED) had a significantly lower cortisol decline throughout the day compared to controls, in both adjusted and unadjusted analyses - Lower cortisol decline among women with a current ED was associated with higher levels of psychopathology during pregnancy - Women's cortisol awakening response, CRH and CRH-BP levels did not differ across the three groups - Infants' stress response was significantly higher among those in the C-ED group, although this effect was attenuated after controlling for confounders
O'Brien et al. (2017)	(37)	To study predictors of self-reported EDs and associations with later health events	Prospective case-control, cohort of sisters of women with breast cancer Controls n = 38,264 EDs n = 726 Puerto-Rican women	EDs were associated with higher rates of miscarriage and induced abortion	Miscarriage: OR 1.19 (95% CI 1.09–1.35) Induced abortion: OR 1.25 (95% CI 1.05–1.5)
Watson et al. (2017)	(99)	To determine if maternal ED increase risk of perinatal events	Retrospective Cohort N = 70,881 pregnancies in grandmother-mother-child triads. Controls (no ED) n = 65,586 Cases n = 5,295 (AN = 409, BN = 1,451, BED = 3,362, Purging disorder = 73). MoBa Cohort	EDs were associated with fetal effects, affecting specially the weight and the gestational age	-AN was associated with: low birth weight (z-score): RR 0.74 (95% CI 0.68, 0.82). SGA: RR 1.54 (95% CI 1.09, 2.17). Postmature: RR 0.47 (95% CI 0.33; 0.67). - BN: Induced labor: RR 1.21 (95% CI 1.07, 1.36). - BED: Birth weight (z-score): RR 1.07 (95% CI 1.05; 1.1). Length > p90: RR 1.2 (95% CI 1.13; 1.28). LGA: RR 1.19 (95% CI 1.14; 1.26)
Paslakis and de Zwaan (2018)	(29)	To review obstetrical and fetal consequences of ED and to present specific clinical recommendations	Review	EDs had negatives effects in obstetrical and fetal outcomes	Higher incidence of miscarriage and induced abortions, premature birth, low birth weight, low Apgar scores, and perinatal death
Eik-nes et al. (2018)	(100)	To identify associations between a lifetime ED (and obstetric outcomes. Adjusted for parity, maternal age, marital status, and year of delivery	Patient ED unit vs. Population-based study (The HUNT Study) from clinical patient register EDs N = 532 vs. unexposed n = 43,567	This study corroborates available evidence on the associations between maternal ED and adverse obstetric outcomes	AN had Higher rate of SGA (OR) 2.7, 95% CI 1.4–5.2. BN showed Higher rate of C- section OR 1.7 95% CI 1.1–2.5
Charbonneau and Seabrook (2019)	(101)	To investigate several adverse birth outcomes associated with Eds during pregnancy: miscarriage, preterm birth (PTB), low birth weight (LBW), SGA, and LGA To assess current ED and past ED	Narrative review (18 studies)	Of the 18 articles reviewed, EDs were associated with preterm birth and small-forgestational-age	- Eds were associated with preterm birth in 5/14 (36%) and SGA in 5/8 (63%) studies - AN increases the odds of a LBW baby, particularly when women enter pregnancy with a low BMI - BED is positively associated with having a LGA infant - BN was associated with miscarriage when symptomatic during pregnancy - Having a current ED increases the risk for adverse birth outcomes more than a past ED
Chan et al. (2019)	(102)	To assess adverse outcomes of EDs in pregnancy, from 1st trimester to 6 months postpartum. Assessment of covariates (BMI, psychological factors, anxiety and depressive symptoms) To assess the association between EDs and risk factors	Prospective longitudinal in a clinical population 1,470 Chinese pregnant women with EDs	Preterm delivery, Apgar scores and BW Disordered eating was assessed with the Eating Attitudes Test-26	- Only smoking before pregnancy was associated with disordered eating symptoms at the third trimester - LGA and low Apgar score were more likely to have mothers with higher levels of disordered eating at T2 and T3 (p < 0.01); - SGA was more likely to have mothers with higher levels of disordered eating at T2 (p < 0.005)
Sotodate et al. (2019)	(103)	To describe one possible fetal consequences of maternal vitamin k deficiency	2 cases reports	The maternal subclinical vitamin K deficiency due to an ED could induce a fetal intracranial hemorrhage	- EDs longer than 3 weeks could develop a maternal subclinical vitamin K deficiency and, consequently, a fetal intracranial hemorrhage - Pregnant women taking drugs inhibiting vitamin K metabolism or intestinal absorption. It must be recommended to take vitamin K from 36 gestational weeks until delivery onset