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. 2019 May 1;11(5):997. doi: 10.3390/nu11050997

Table 1.

Summary of the included studies.

Author Geographic Area Study Design Included Participants Assessment of Dietary Habits Assessment of Adherence to MD Outcomes Results
Timmermans et al.
(2012) [38]
Netherlands Prospective population-based cohort study 3207 mothers with a spontaneously conceived live-born singleton pregnancy Semi-quantitative FFQ (293 items) self-administered during early pregnancy (GA < 18 weeks) Logistic regression analysis was used to identify a comparable dietary pattern, which was labeled MD as it was characterized by higher intakes of pasta, rice, vegetable oils, fish, vegetables and alcohol, and lower intakes of meat, potatoes and fatty sauces. All women were categorized into equal tertiles based on their probability score for the diet, namely: low MDA, medium MDA and high MDA. Fetal growth Low MDA resulted associated with lower birth weight (difference in grams at birth −72 [95% CI: −110.8 to 33.3])
Chatzi et al.
(2012) [39]
Spain (INMA cohort) and Greece (RHEA cohort) Prospective population-based cohort study Spain: 2461 mother-newborn pairs. Greece: 889 mother-newborn pairs Semi-quantitative FFQ (100 items in IMNA cohort and 250 items in RHEA cohort) administered by trained interviewers during first (IMNA cohort) or mid trimester (RHEA cohort) of pregnancy Trichopoulou’s score [40] modified for pregnancy Fetal growth High MDA was associated with lower risk of delivering a FGR infant (OR 0.5 [95% CI: 0.3–0.9]) in the INMA-Mediterranean cohort. In all cohort high MD adherence increased birth weight in smoking mothers
Sauders et al.
(2014) [41]
Guadeloupe (French Caribbean Island) Prospective mother-child cohort study 728 pregnant women with a live-born singleton pregnancy without major congenital malformations Semi-quantitative FFQ (214 items) administered by trained interviewers in the days after delivery Trichopoulou’s score [40] Fetal growth and prematurity No overall associations with FGR. No overall association with prematurity. Decreased risk in overweight and obese woman (adjOR 0.7 [95% CI: 0.6–0.9])
Gomez-Roig et al.
(2017) [42]
Spain Cross-sectional study 46 mothers with SGA fetuses
81 mothers with appropriate for gestational age (AGA) fetuses
Semi-quantitative FFQ (127 items) administered by trained interviewers during the third trimester of pregnancy Trichopoulou’s score [40] SGA infants High MD score was associated with a lower risk of SGA (OR 0.18 [95% CI: 0.74–0.501]) for the third consumer quartile
Peraita-Costa et al.
(2018) [43]
Spain Cross-sectional population-based study 492 mothers Semi-quantitative FFQ (16 items) self-administered after delivery Modified KidMed score [44] SGA infants The newborns born to women with low MDA presented a higher risk of being SGA (adjOR 1.68 [95% CI: 1.02–5.46]) when adjusting for parental BMI and multiple gestation, but not when adjusting for all significant possible confounders.
Parlapani et al.
(2017) [45]
Greece Single-center, prospective, observational cohort study 82 women who delivered preterm singletons at post conceptional age < 34 weeks Semi-quantitative FFQ (156 items) self-administered immediately before or after delivery Panagiotakos dietary score [46] Fetal growth and prematurity-associated complications Low MD adherence increased the risk of IUGR, low birth weight, bronchopulmonary dysplasia and necrotizing enterocolitis in preterm infants (<34 weeks)
Martinez-Galiano et al.
(2018) [47]
Spain Prospective multicenter matched case-control study (matching criterion: maternal age at delivery) 518 mothers of singleton SGA infants
518 mothers of singleton infants with normal weight for GA
Semi-quantitative FFQ (137 items) administered by trained interviewers within 2 days after delivery PREDIMED score [48], Trichopoulou’s score [40], Panagiotakos’ score [46] SGA infants MDA and daily consumption of 5 gr of olive oil was associated to a reduced risk of SGA in newborns (adjOR 0.59 [95% CI: 0.38–0.98])
Assaf-Balut et al.
(2017) [49]
Spain Prospective randomized controlled intervention trial 500 mothers allocated to intervention (MD diet supplemented with extra virgin olive oil and pistachios) and 500 allocated to control (standard diet with limited fat intake) Semi-quantitative FFQ (14 items) administered by trained interviewed during 4 study visits (at first ultrasound visit at 24–28 GA, at 36–38 GA, and at delivery) to evaluate the adherence to the intervention MDA screener score [50] SGA infants and prematurity MD supplemented with extravergin olive oil and pistachios significantly reduced prematurity rate (p 0.023) and SGA (p 0.001) in the intervention group
Carmichael et al.
(2013) [51]
United States Cross-sectional study 5738 mothers with a singleton pregnancy who delivered non-malformed infants Semi-quantitative FFQ (58 items) administered by telephone interview 6 weeks—24 months after delivery Trichopoulou’s score [40] and DQI incorporating pregnancy-specific nutritional recommendations [52] Prematurity No association
Mikkelse et al.
(2008) [53]
Denmark Prospective cohort study 35657 pregnant women with a live-born singleton pregnancy Semi-quantitative FFQ (360 items) self-administered at mid-pregnancy (week 25) by mail Khoury’s score [54] Prematurity High MDA reduced the risk of early preterm birth (adjOR 0.28 [95% CI: 0.11–0.76]). No associations with late preterm delivery.
Haugen et al.
(2008) [55]
Norway Prospective cohort study 26563 pregnant women with a live-born singleton pregnancy Semi-quantitative FFQ (255 items) self-administered at week 18–22 of pregnancy Khoury’s score [54] Prematurity No association
Smith et al.
(2015) [56]
United Kingdom Population-based cohort study 922 mothers with singleton late and moderate preterm (LMPT) births
965 mothers with singleton term births
Maternal interview shortly after delivery MDA on the basis of the presence of at least 1 of the following major criteria: five portions of fruit and vegetables every day; fish more than twice a week; meat no more than twice a week; max two cups of coffee/d. Late and moderately preterm (LMPT) birth Higher risk of delivering LMPT in not adherent women (RR 1.81 [95% CI: 1.04–3.14])
Vujkovic et al.
(2009) [57]
Netherlands Retrospective multicenter case-control study 50 mothers of children with spina bifida
81 control mothers
Semi-quantitative FFQ (200 items) administered 14 months after delivery and individually checked for consistency at the hospital or by telephone by the researcher. Principal component factor analysis (PCA) and reduce rank regression (RRR) were used to identify a comparable dietary pattern, which was labeled MD as it was characterized by high intake of vegetables, fruits, vegetable oils, legumes, fish, alcohol and cereal products and low intakes of potatoes and sweets. NTDs Low MDA according to both PCA and RRR, was associated with an increased risk of spina bifida (OR 2.7 [95% CI: 1.2–6.1] and OR 3.5 [95% CI: 1.5–7.9], respectively)
Carmicheal et al.
(2012) [58]
United States Retrospective multicenter case-control study 936 mothers of children with NTDs
2475 mothers of children with orofacial clefts
6147 control mothers
Semi-quantitative FFQ (58 items) administered by telephone interviews 6 weeks–24 months after delivery Trichopoulou’s score [40] and DQI [52] incorporating pregnancy-specific nutritional recommendations NTDs and orofacial clefts High Trichopoulou score and DQI score were protective for NTDs, with a stronger association observed for anencephaly (adjOR 0.64 [95% CI: 0.45–0.92] and 0.49 [95% CI: 0.31–0.75], respectively)
Botto et al.
(2016) [59]
USA Population based, multicenter case-control study 9885 case mothers
9468 control mothers
Semi-quantitative FFQ (58 items) administered by telephone interviews 6 weeks–24 months after delivery Trichopoulou’s score [40] and the DQI [52] incorporating pregnancy-specific nutritional recommendations Congenital Heart Defects High Trichopoulou’s score was protective only for perimembranous ventricular septal defects (14%, OR 0.86 [95% CI: 0.69–1.07]). High DQI was protective for tetralogy of Fallot (OR 0.63 [95% CI: 0.49–0.80]), conotruncal defects (OR 0.76 [95% CI: 0.64–0.91]), atrial septal defects (OR 0.77 [95% CI: 0.63–0.94]) and for all septal defects (OR 0.86 [95% CI: 0.75–1.00]).
Feldkamp et al.
(2014) [60]
USA Population based, multicenter case-control study 1125 gastroschisis cases
9483 controls
58-item FFQ (58 items) administered by a computerized-assisted telephone interview
(CATI) to case and control mothers 6wk to 24 months
delivery
Trichopoulou’s score [40] and the DQI [52] incorporating pregnancy-specific nutritional recommendations Gastroschisis High Trichopoulou’s score (quartile 2, adjOR0.62 [95% CI: 0.33–1.16]; quartile 3, adjOR0.51 [95% CI: 0.28–0.94]; quartile 4, adjOR0.50 [95% CI: 0.28, 0.90]) and DQI score (quartile 2, adjOR 0.58 [95% CI: 0.40–0.86]; quartile 3, adjOR 0.52 [95% CI: 0.36–0.79]; quartile 4, adjOR 0.48 [95% CI: 0.32–0.76]) were protective for gastroschisis.
Chatzi et al.
(2008) [61]
Spain Cohort study 460 children Semi-quantitative FFQ (42 items) referred to the pregnancy and administered to mothers 3 months after delivery by a face-to-face interview. Semi-quantitative FFQ (96 items) administered to the parents of the children at 6.5 year of age by an interviewer Trichopoulou’s score [40] Wheeze, atopic wheeze and atopy at 6.5 years High MDS in mothers was protective for persistent wheeze (adjOR 0.22 [95% CI:0.08–0.58]), atopic wheeze (adjOR0.30 [95% CI:0.10–0.90]), and atopy (adjOR 0.55 [95% CI: 0.31–0.97]) in children at 6,5 years
De Batlle et al.
(2008) [62]
Mexico Cross-sectional study 1476 children Semi-quantitative FFQ (70 items) referred to the pregnancy and self-administered at the children age of 6–7 years Trichopoulou’s score [40] Asthma, Wheezing, rhinitis, sneezing, itchy-watery eyes at 6-7 years High MDS was protective for current sneezing (OR 0.71 [95% CI: 0.53–0.97]).
Castro-Rodriguez et al.
(2010) [63]
Spain Cohort study 1409 infants Semi-quantitative FFQ (11 items) referred to the pregnancy and self-administered at the children’s aged of 15–18 months MDS modified from Psaltopoulou [64] Wheeze at 12 months MD (p 0.036) and olive oil (p 0.002) were associated with less wheezing. Only olive oil intake remained inversely associated with wheezing (adjOR 0.57 [95% CI: 0.4–0.9])
Chatzi et al.
(2013) [65]
Spain (INMA cohort) and Greece (RHEA cohort) Cohort study Spain:
1771 mother-newborn pairs. Greece:
745 mother-newborn pairs
Semi-quantitative FFQ (100 items in IMNA cohort and 250 items in RHEA cohort) administered by trained interviewers at mean 13.8 weeks of GA (IMNA cohort) or 14.6 weeks of GA (RHEA cohort) Trichopoulou’s score [40] modified for pregnancy considering dairy food protective and not including in the score alcohol consumption. Wheeze and eczema at 12 months No associations between MD score and wheeze and eczema
Alvarez-Zallo et al.
(2018) [66]
Spain Cohort study 1087 mother-infant pairs Semi-quantitative FFQ (11-items) referred to the pregnancy and self-administered at the children aged 12–15 months MDS modified from Psaltopoulou [64] Wheeze and eczema at 12–15 months No associations between MD score and wheezing, recurrent wheezing and eczema
Lange et al.
(2010) [67]
United States Cohort study 1376 mother-infant pairs Semi-quantitative FFQ (166 items) self-administered at the first and second trimesters visits MD score modified from Trichopoulou [40], Alternate Healthy Eating Index modified for pregnancy [68] and PCA to look at Western and Prudent diets Wheeze, asthma and atopy at 3 years No associations between dietary patterns and asthma, atopy or wheezing
Castro-Rodriguez et al.
(2016) [69]
Spain Cohort study 1000 mother-newborn pairs Semi-quantitative FFQ (11 items) regarding the consumption of foods during pregnancy self-administered at the time point of 1.5 years of children’s life. Semi-quantitative FFQ (11 items) regarding the consumption of food by the child self-administered at the time point of 4 years of life MDS modified from Psaltopoulou [64] Wheeze, dermatitis and allergic rhinitis at 4 years No associations between MD score and wheezing, rhinitis and dermatitis
Gesteiro et al.
(2012) [70]
Spain Cross sectional study 35 women 169 items FFQ conducted by a trained dietician 3–5 after delivery Healthy eating index (HEI) adapted for the Spanish population [71] and by a modified MDA scores used in the PREDIMED study [72] Various insulin sensitivity/resistance biomarkers at birth Low HEI- or low MDA-score diet delivered infants with high insulinaemia (p 0.048 or p 0.017, respectively), HOMA-IR (p 0.031 or p 0.049, respectively) and glycaemia (p 0.018 or p 0.048, respectively). The relative risk (RR) of high-neonatal glycaemia and insulinaemia were 7.6 (p 0.008) and 6.7 (p 0.017) for low vs. high HEI-score groups. High HOMA-IR and high glucose RR were, respectively, 3.4 (p 0.043) and 3.9 (p 0.016) in neonates from the <7 MDA- vs. >7 MDA-score group.
Chatzi et al.
(2017) [73]
USA (Project Viva cohort) and Greece (RHEA cohort) Prospective mother–child cohort study 997 mother–child pairs from Project Viva and 569 pairs from the RHEA study In Project Viva, mothers reported their diet since the time of their last menstrual period at study enrolment (median 9.9 weeks gestation) using a validated semi-quantitative FFQ. RHEA participants completed a validated FFQ at mean 14.6 weeks gestation. Trichopoulou’s score [40] BMI z-score, waist circumference, skin-fold thickness, systolic and diastolic blood pressure In the pooled analysis, for each 3-point increment in the MDS, offspring BMI z-score was lower by 0.14 units (95% CI: −0.15 to −0.13), waist circumference by 0.39cm (95% CI: −0.64 to −0.14), the sum of skin-fold thicknesses by 0.63mm (95% CI: 0.98 to −0.28), systolic blood pressure by −1.03 mmHg (95% CI: −1.65 to −0.42) and diastolic blood pressure by −0.57 mmHg (95% CI: −0.98 to −0.16).
Fernández-Barrés et al.
(2016) [74]
Spain Population based cohort study 1827 pairs of mother and children Validated 101 items FFQ conducted from first to third trimester RelativeMediterranean diet score (rMED) [75] BMI and waist circumference A significant association between higher adherence to MD and lower waist circumference (−0.62 cm [95% CI: −1.1 to −0.14]).
Gesteiro et al.
(2015) [76]
Spain Cross sectional study 35 women Complete 169 items FFQ guided by a trained dietician conducted at first trimester Modified MDA scores used in the PREDIMED study [72] Cord blood lipoprotein and homocysteine concentrations Mothers at the low MDA-score delivered neonates with high cord blood LDL-c (p 0.049), Apo B (p 0.040), homocysteine (p 0.026) and Apo A1/Apo B ratio (p 0.024).
Mantzoros et al.
(2010) [77]
USA Prospective cohort study 780 women Slightly modified semi-quantitative FFQ at both the first and second trimester Trichopoulou’s score [40] Cord blood leptin and adiponectin concentrations Closer adherence to a Mediterranean pattern diet during pregnancy was not associated with cord blood leptin (p 0.38) or adiponectin (p 0.93)
Gonzalez-Nahm et al.
(2017) [78]
USA Cohort study 390 women whose infants had DNA methylation data available from cord blood leukocytes 150 items FFQ at preconception or at first trimester Modified Trichopoulou’s score [40] Methylation at the MEG3-IG region Infants of mothers with a low adherence to a Mediterranean diet had a greater odd of hypo-methylation at the MEG3-IG differentially methylated region (OR 2.80 [95% CI: 1.35−5.82])

adjOR: adjusted odds ratio; BMI: body mass index; CI: confidence interval; GA: gestational age; FFQ: food frequency questionnaire; MEG3-IG: maternally expressed gene 3 - intergenic region; MD: Mediterranean Diet; MDA: Mediterranean Diet adherence; NTDs: neural tube defects; OR odds ratio; PTD: preterm delivery; RR: relative risk; SGA: small for gestational age; LMPT: Late and moderately preterm; HOMA-IR: homeostatic model assessment for insulin resistance.